<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2024 Workiva-->
<!--r:b3dee001-f8fc-4552-b71c-248998c75797,g:81096e15-be24-44c5-a056-6ee5f463d4d7-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/ConsolidatedStatementsofStockholdersEquity" xlink:type="simple" xlink:href="arwr-20231231.xsd#ConsolidatedStatementsofStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/ConsolidatedStatementsofStockholdersEquity" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_3c0209a3-7b10-42e7-b4fc-d9d13f7d0ca1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_b4372782-1668-419e-8d38-da6571c38852" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_3c0209a3-7b10-42e7-b4fc-d9d13f7d0ca1" xlink:to="loc_us-gaap_StatementTable_b4372782-1668-419e-8d38-da6571c38852" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_7c2a5ac9-d3e6-47c3-b7ba-d11d57d278d7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_b4372782-1668-419e-8d38-da6571c38852" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_7c2a5ac9-d3e6-47c3-b7ba-d11d57d278d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_7c2a5ac9-d3e6-47c3-b7ba-d11d57d278d7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_7c2a5ac9-d3e6-47c3-b7ba-d11d57d278d7" xlink:to="loc_us-gaap_EquityComponentDomain_7c2a5ac9-d3e6-47c3-b7ba-d11d57d278d7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_4bd4dadd-4753-4cb5-bf9c-1b7181f48989" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_7c2a5ac9-d3e6-47c3-b7ba-d11d57d278d7" xlink:to="loc_us-gaap_EquityComponentDomain_4bd4dadd-4753-4cb5-bf9c-1b7181f48989" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_081d1595-ffb3-4319-8786-9f213cde07b2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_4bd4dadd-4753-4cb5-bf9c-1b7181f48989" xlink:to="loc_us-gaap_CommonStockMember_081d1595-ffb3-4319-8786-9f213cde07b2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_9e2f1ada-f7d6-4a7a-80d9-b6e04d81c96e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_4bd4dadd-4753-4cb5-bf9c-1b7181f48989" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_9e2f1ada-f7d6-4a7a-80d9-b6e04d81c96e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_1808c100-1571-444d-8b2f-8ac1a80b8078" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_4bd4dadd-4753-4cb5-bf9c-1b7181f48989" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_1808c100-1571-444d-8b2f-8ac1a80b8078" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_a61d4a31-12a6-4d5b-933e-1a8b709f2813" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_4bd4dadd-4753-4cb5-bf9c-1b7181f48989" xlink:to="loc_us-gaap_RetainedEarningsMember_a61d4a31-12a6-4d5b-933e-1a8b709f2813" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NoncontrollingInterestMember_ae90466f-7bb2-4d36-81c5-994b6c718890" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NoncontrollingInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_4bd4dadd-4753-4cb5-bf9c-1b7181f48989" xlink:to="loc_us-gaap_NoncontrollingInterestMember_ae90466f-7bb2-4d36-81c5-994b6c718890" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_3c0209a3-7b10-42e7-b4fc-d9d13f7d0ca1" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_cafc4944-a169-4ac6-84a2-a0c8994719dc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_cafc4944-a169-4ac6-84a2-a0c8994719dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_898316e5-a06b-4316-bbeb-a774415ff320" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_SharesOutstanding_898316e5-a06b-4316-bbeb-a774415ff320" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_8302d219-f455-43c4-b793-eda0dc6f9039" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_8302d219-f455-43c4-b793-eda0dc6f9039" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_7052ee3d-43e1-44f6-8584-350824804084" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_7052ee3d-43e1-44f6-8584-350824804084" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_d00c51aa-0040-4ee4-be25-8f4e4b095e91" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_d00c51aa-0040-4ee4-be25-8f4e4b095e91" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_97c641fb-9219-424d-908c-e513034b84fb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_97c641fb-9219-424d-908c-e513034b84fb" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_5c9bf678-b9ea-42fb-bd15-917c0f696f80" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_5c9bf678-b9ea-42fb-bd15-917c0f696f80" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_9730cae0-5348-4d23-b0be-abc04d8e7b3f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_9730cae0-5348-4d23-b0be-abc04d8e7b3f" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_14a624e6-a5fa-4302-a108-c012b10fbf79" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_14a624e6-a5fa-4302-a108-c012b10fbf79" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProfitLoss_fda0ce47-e957-474a-9648-2ce3f20f7dfc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProfitLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_3bdbc2dd-cbcf-42ce-a290-905c5b62fd93" xlink:to="loc_us-gaap_ProfitLoss_fda0ce47-e957-474a-9648-2ce3f20f7dfc" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_38c078cb-7c63-47b1-884c-d6f97fc5499b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_8cc98695-e392-4cc6-9fb7-35332bcbd859" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesOutstanding"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/OrganizationandSignificantAccountingPoliciesAdditionalInformationDetail" xlink:type="simple" xlink:href="arwr-20231231.xsd#OrganizationandSignificantAccountingPoliciesAdditionalInformationDetail"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/OrganizationandSignificantAccountingPoliciesAdditionalInformationDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:href="arwr-20231231.xsd#arwr_OrganizationAndSignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_cbe97326-54dc-46c9-a37c-a767ca30e4f5" xlink:href="arwr-20231231.xsd#arwr_OrganizationAndSignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_cbe97326-54dc-46c9-a37c-a767ca30e4f5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_42256c6c-49cb-445e-b08b-74e37e4f76d4" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_cbe97326-54dc-46c9-a37c-a767ca30e4f5" xlink:to="loc_srt_CounterpartyNameAxis_42256c6c-49cb-445e-b08b-74e37e4f76d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_42256c6c-49cb-445e-b08b-74e37e4f76d4_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_42256c6c-49cb-445e-b08b-74e37e4f76d4" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_42256c6c-49cb-445e-b08b-74e37e4f76d4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_dc86dab0-7673-4cc5-9916-cd3a5b4d850d" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_42256c6c-49cb-445e-b08b-74e37e4f76d4" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_dc86dab0-7673-4cc5-9916-cd3a5b4d850d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_RoyaltyPharmaMember_8a8d0901-9406-4e26-be81-4c7e97168fd3" xlink:href="arwr-20231231.xsd#arwr_RoyaltyPharmaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_dc86dab0-7673-4cc5-9916-cd3a5b4d850d" xlink:to="loc_arwr_RoyaltyPharmaMember_8a8d0901-9406-4e26-be81-4c7e97168fd3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_8eb71c8c-b1db-42ae-9f24-29101e3f9c03" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_cbe97326-54dc-46c9-a37c-a767ca30e4f5" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_8eb71c8c-b1db-42ae-9f24-29101e3f9c03" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_8eb71c8c-b1db-42ae-9f24-29101e3f9c03_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_8eb71c8c-b1db-42ae-9f24-29101e3f9c03" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_8eb71c8c-b1db-42ae-9f24-29101e3f9c03_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_2f5f4874-db59-4e61-9b33-2b25e86497e8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_8eb71c8c-b1db-42ae-9f24-29101e3f9c03" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_2f5f4874-db59-4e61-9b33-2b25e86497e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_2dd75c25-0be5-4b23-b0ff-c4b14f7d106b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_2f5f4874-db59-4e61-9b33-2b25e86497e8" xlink:to="loc_us-gaap_SubsequentEventMember_2dd75c25-0be5-4b23-b0ff-c4b14f7d106b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_42de536d-84de-4233-9729-904ca1b2ee30" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_cbe97326-54dc-46c9-a37c-a767ca30e4f5" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_42de536d-84de-4233-9729-904ca1b2ee30" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_42de536d-84de-4233-9729-904ca1b2ee30_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_42de536d-84de-4233-9729-904ca1b2ee30" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_42de536d-84de-4233-9729-904ca1b2ee30_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_1ff3a3bc-3b32-4e93-9aba-c886d88a48ff" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_42de536d-84de-4233-9729-904ca1b2ee30" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_1ff3a3bc-3b32-4e93-9aba-c886d88a48ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_UnderwritingAgreementMember_671c311b-4415-4499-8cb7-8672c1e71369" xlink:href="arwr-20231231.xsd#arwr_UnderwritingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_1ff3a3bc-3b32-4e93-9aba-c886d88a48ff" xlink:to="loc_arwr_UnderwritingAgreementMember_671c311b-4415-4499-8cb7-8672c1e71369" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_1aa6582d-7dc5-4d58-86a3-a8591be9b7ad" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_1aa6582d-7dc5-4d58-86a3-a8591be9b7ad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_d3e65111-f78c-4cb1-96ae-bee722e837a4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_d3e65111-f78c-4cb1-96ae-bee722e837a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_bbca0c29-a01c-4f93-b880-6ee0a4a9926a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_bbca0c29-a01c-4f93-b880-6ee0a4a9926a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_IncreaseDecreaseInCashAndInvestments_405ba4bc-d666-4faa-845c-5b608f473639" xlink:href="arwr-20231231.xsd#arwr_IncreaseDecreaseInCashAndInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_arwr_IncreaseDecreaseInCashAndInvestments_405ba4bc-d666-4faa-845c-5b608f473639" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_UpfrontMilestonePaymentReceived_1e23859d-7d0e-4379-b97a-031a9e024ed0" xlink:href="arwr-20231231.xsd#arwr_UpfrontMilestonePaymentReceived"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_arwr_UpfrontMilestonePaymentReceived_1e23859d-7d0e-4379-b97a-031a9e024ed0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_3d2dee63-44d5-4a2d-aa48-3ad7b98c342f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_3d2dee63-44d5-4a2d-aa48-3ad7b98c342f" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_9dff04f5-f064-4d73-9b98-8a8e1d28708b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_9dff04f5-f064-4d73-9b98-8a8e1d28708b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SaleOfStockAggregatePurchasePrice_cdbffe83-e878-4efe-af3f-0ca4c4938310" xlink:href="arwr-20231231.xsd#arwr_SaleOfStockAggregatePurchasePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_arwr_SaleOfStockAggregatePurchasePrice_cdbffe83-e878-4efe-af3f-0ca4c4938310" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_22bc8292-93cd-4cf0-802b-bb40681b3c8a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_22bc8292-93cd-4cf0-802b-bb40681b3c8a" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_e9224382-a8b5-4294-af03-ff43b17ce16a" xlink:href="arwr-20231231.xsd#arwr_DevelopmentRegulatoryAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_e9224382-a8b5-4294-af03-ff43b17ce16a" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_4e9ebd65-d7bb-425a-ae7e-e714a67acfa4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_2edf453f-ce93-4f07-9c22-3d1e47b6ca07" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_4e9ebd65-d7bb-425a-ae7e-e714a67acfa4" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsRevenueDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#CollaborationandLicenseAgreementsRevenueDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsRevenueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_118a91e7-d8a1-4f59-9dc6-86039027cb16" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_23d19ddb-ad97-44d6-b2fa-9470c308486e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_118a91e7-d8a1-4f59-9dc6-86039027cb16" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_23d19ddb-ad97-44d6-b2fa-9470c308486e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_2bfd664e-7e23-4514-8bbf-61791f2f3a65" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_23d19ddb-ad97-44d6-b2fa-9470c308486e" xlink:to="loc_srt_MajorCustomersAxis_2bfd664e-7e23-4514-8bbf-61791f2f3a65" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_2bfd664e-7e23-4514-8bbf-61791f2f3a65_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_2bfd664e-7e23-4514-8bbf-61791f2f3a65" xlink:to="loc_srt_NameOfMajorCustomerDomain_2bfd664e-7e23-4514-8bbf-61791f2f3a65_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_55543651-11c5-47bf-994b-766216da7c87" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_2bfd664e-7e23-4514-8bbf-61791f2f3a65" xlink:to="loc_srt_NameOfMajorCustomerDomain_55543651-11c5-47bf-994b-766216da7c87" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_3c9e26e3-52ef-4e10-bd9c-6a4baa588ae8" xlink:href="arwr-20231231.xsd#arwr_GlaxosmithklineIntellectualPropertyLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_55543651-11c5-47bf-994b-766216da7c87" xlink:to="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_3c9e26e3-52ef-4e10-bd9c-6a4baa588ae8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_HorizonTherapeuticsIrelandDACMember_82077d96-03e1-48cd-83c6-af93f2c7b145" xlink:href="arwr-20231231.xsd#arwr_HorizonTherapeuticsIrelandDACMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_55543651-11c5-47bf-994b-766216da7c87" xlink:to="loc_arwr_HorizonTherapeuticsIrelandDACMember_82077d96-03e1-48cd-83c6-af93f2c7b145" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_c3f183bb-e864-4f97-86f2-fd5e1222de70" xlink:href="arwr-20231231.xsd#arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_55543651-11c5-47bf-994b-766216da7c87" xlink:to="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_c3f183bb-e864-4f97-86f2-fd5e1222de70" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_JanssenPharmaceuticalsIncorporationMember_3f32f126-c8e1-4a63-8f1d-74d26a424355" xlink:href="arwr-20231231.xsd#arwr_JanssenPharmaceuticalsIncorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_55543651-11c5-47bf-994b-766216da7c87" xlink:to="loc_arwr_JanssenPharmaceuticalsIncorporationMember_3f32f126-c8e1-4a63-8f1d-74d26a424355" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AmgenIncorporatedMember_a8f2d6b4-e528-4cb3-83e3-6eb3f2ebb110" xlink:href="arwr-20231231.xsd#arwr_AmgenIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_55543651-11c5-47bf-994b-766216da7c87" xlink:to="loc_arwr_AmgenIncorporatedMember_a8f2d6b4-e528-4cb3-83e3-6eb3f2ebb110" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_2fc31193-d530-43be-92ff-4c894ab6877f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_118a91e7-d8a1-4f59-9dc6-86039027cb16" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_2fc31193-d530-43be-92ff-4c894ab6877f" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsGlaxosmithklineIntellectualPropertyNo3LimitedDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#CollaborationandLicenseAgreementsGlaxosmithklineIntellectualPropertyNo3LimitedDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsGlaxosmithklineIntellectualPropertyNo3LimitedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_0dff8c56-f595-4461-b3ca-430359398070" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_0dff8c56-f595-4461-b3ca-430359398070" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_9abdef5e-2368-404d-866e-490f66d8ed27" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_0dff8c56-f595-4461-b3ca-430359398070" xlink:to="loc_srt_CounterpartyNameAxis_9abdef5e-2368-404d-866e-490f66d8ed27" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9abdef5e-2368-404d-866e-490f66d8ed27_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_9abdef5e-2368-404d-866e-490f66d8ed27" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9abdef5e-2368-404d-866e-490f66d8ed27_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_751f645c-90ed-4493-b119-e602769b0f25" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_9abdef5e-2368-404d-866e-490f66d8ed27" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_751f645c-90ed-4493-b119-e602769b0f25" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_4bd6048e-b35d-466c-b9db-bd5fa6cad48e" xlink:href="arwr-20231231.xsd#arwr_GlaxosmithklineIntellectualPropertyLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_751f645c-90ed-4493-b119-e602769b0f25" xlink:to="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_4bd6048e-b35d-466c-b9db-bd5fa6cad48e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_602e59e8-b172-48cb-9776-5bac50f1dfb8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_0dff8c56-f595-4461-b3ca-430359398070" xlink:to="loc_us-gaap_TypeOfArrangementAxis_602e59e8-b172-48cb-9776-5bac50f1dfb8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_602e59e8-b172-48cb-9776-5bac50f1dfb8_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_602e59e8-b172-48cb-9776-5bac50f1dfb8" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_602e59e8-b172-48cb-9776-5bac50f1dfb8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ce49ceee-9e50-4e1e-8678-f994b71a6765" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_602e59e8-b172-48cb-9776-5bac50f1dfb8" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ce49ceee-9e50-4e1e-8678-f994b71a6765" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GSKLicenseAgreementMember_6002fd9d-31ca-4f52-99d9-ee5da50406f8" xlink:href="arwr-20231231.xsd#arwr_GSKLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ce49ceee-9e50-4e1e-8678-f994b71a6765" xlink:to="loc_arwr_GSKLicenseAgreementMember_6002fd9d-31ca-4f52-99d9-ee5da50406f8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GSKHBVAgreementMember_b2c68b75-f7ea-4c1e-b76b-b26a79e9212e" xlink:href="arwr-20231231.xsd#arwr_GSKHBVAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ce49ceee-9e50-4e1e-8678-f994b71a6765" xlink:to="loc_arwr_GSKHBVAgreementMember_b2c68b75-f7ea-4c1e-b76b-b26a79e9212e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_e6eada90-2014-4c16-a938-e83c5a83c603" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_0dff8c56-f595-4461-b3ca-430359398070" xlink:to="loc_srt_RangeAxis_e6eada90-2014-4c16-a938-e83c5a83c603" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_e6eada90-2014-4c16-a938-e83c5a83c603_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_e6eada90-2014-4c16-a938-e83c5a83c603" xlink:to="loc_srt_RangeMember_e6eada90-2014-4c16-a938-e83c5a83c603_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_be54f468-3e20-40ce-bb58-ae1bcb4d10db" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_e6eada90-2014-4c16-a938-e83c5a83c603" xlink:to="loc_srt_RangeMember_be54f468-3e20-40ce-bb58-ae1bcb4d10db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_32dd9504-4d48-41ff-b6ac-969678b254a4" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_be54f468-3e20-40ce-bb58-ae1bcb4d10db" xlink:to="loc_srt_MaximumMember_32dd9504-4d48-41ff-b6ac-969678b254a4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivable_2bd3784a-bdb2-4f3e-abfa-561f98117a19" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_arwr_MilestonePaymentReceivable_2bd3784a-bdb2-4f3e-abfa-561f98117a19" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponAchievementOfPhaseTwoAndFirstPatientDosedInPhaseThree_16bd1564-c2ef-43bc-91a0-1b6cbc5c73bc" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentReceivableUponAchievementOfPhaseTwoAndFirstPatientDosedInPhaseThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_arwr_MilestonePaymentReceivableUponAchievementOfPhaseTwoAndFirstPatientDosedInPhaseThree_16bd1564-c2ef-43bc-91a0-1b6cbc5c73bc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommercialMilestonePaymentsAtFirstCommercialSale_82e32ea2-17ca-42ad-85d6-ec0bb9db8ec4" xlink:href="arwr-20231231.xsd#arwr_CommercialMilestonePaymentsAtFirstCommercialSale"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_arwr_CommercialMilestonePaymentsAtFirstCommercialSale_82e32ea2-17ca-42ad-85d6-ec0bb9db8ec4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SalesRelatedMilestonePayments_6a0c36fb-ca25-4f75-9abc-a4679e5cdf1a" xlink:href="arwr-20231231.xsd#arwr_SalesRelatedMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_arwr_SalesRelatedMilestonePayments_6a0c36fb-ca25-4f75-9abc-a4679e5cdf1a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_46765811-06e8-4481-8ea7-c2f127c18102" xlink:href="arwr-20231231.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_arwr_InitialTransactionPrice_46765811-06e8-4481-8ea7-c2f127c18102" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DevelopmentAndSalesMilestonesPayments_79607218-ab90-4c46-87b3-5ee2a52622f1" xlink:href="arwr-20231231.xsd#arwr_DevelopmentAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_arwr_DevelopmentAndSalesMilestonesPayments_79607218-ab90-4c46-87b3-5ee2a52622f1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerAssetNetCurrent_e300c61e-2683-48a0-9089-a359806fa718" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerAssetNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_us-gaap_ContractWithCustomerAssetNetCurrent_e300c61e-2683-48a0-9089-a359806fa718" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_546c85d2-91d1-48ed-808f-19810a8764f4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9464f11a-f3b3-4e89-a9ee-ad9eafb23b1e" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_546c85d2-91d1-48ed-808f-19810a8764f4" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsHorizonTherapeuticsIrelandDACDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#CollaborationandLicenseAgreementsHorizonTherapeuticsIrelandDACDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsHorizonTherapeuticsIrelandDACDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d4400325-3a47-4cbe-a69c-93b6969bdddb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_42248699-41ff-4942-bcd8-18ad4220556c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d4400325-3a47-4cbe-a69c-93b6969bdddb" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_42248699-41ff-4942-bcd8-18ad4220556c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_d87fc6a2-6751-4207-bde4-75dbe53f41b9" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_42248699-41ff-4942-bcd8-18ad4220556c" xlink:to="loc_srt_CounterpartyNameAxis_d87fc6a2-6751-4207-bde4-75dbe53f41b9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d87fc6a2-6751-4207-bde4-75dbe53f41b9_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_d87fc6a2-6751-4207-bde4-75dbe53f41b9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d87fc6a2-6751-4207-bde4-75dbe53f41b9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f8c47cd8-d7a0-4bcc-882f-bde7c362be0b" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_d87fc6a2-6751-4207-bde4-75dbe53f41b9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f8c47cd8-d7a0-4bcc-882f-bde7c362be0b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_HorizonTherapeuticsIrelandDACMember_9d150fae-9902-4caa-bbd5-894105f3c6d9" xlink:href="arwr-20231231.xsd#arwr_HorizonTherapeuticsIrelandDACMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f8c47cd8-d7a0-4bcc-882f-bde7c362be0b" xlink:to="loc_arwr_HorizonTherapeuticsIrelandDACMember_9d150fae-9902-4caa-bbd5-894105f3c6d9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_ea7979e4-936e-4414-b5aa-0f326812ddab" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_42248699-41ff-4942-bcd8-18ad4220556c" xlink:to="loc_us-gaap_TypeOfArrangementAxis_ea7979e4-936e-4414-b5aa-0f326812ddab" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ea7979e4-936e-4414-b5aa-0f326812ddab_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_ea7979e4-936e-4414-b5aa-0f326812ddab" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ea7979e4-936e-4414-b5aa-0f326812ddab_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a690e92f-fe58-470f-acaf-4d3f66d7727b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_ea7979e4-936e-4414-b5aa-0f326812ddab" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a690e92f-fe58-470f-acaf-4d3f66d7727b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_HorizonLicenseAgreementMember_46c813cf-0384-42c7-bf09-c91c022c6bbe" xlink:href="arwr-20231231.xsd#arwr_HorizonLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a690e92f-fe58-470f-acaf-4d3f66d7727b" xlink:to="loc_arwr_HorizonLicenseAgreementMember_46c813cf-0384-42c7-bf09-c91c022c6bbe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfDistinctPerformanceObligations_aa2a7628-d808-4e98-a3a7-37aa6f6c03ad" xlink:href="arwr-20231231.xsd#arwr_NumberOfDistinctPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d4400325-3a47-4cbe-a69c-93b6969bdddb" xlink:to="loc_arwr_NumberOfDistinctPerformanceObligations_aa2a7628-d808-4e98-a3a7-37aa6f6c03ad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_ca62358b-5bfa-4462-8aa8-d5a86300b063" xlink:href="arwr-20231231.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d4400325-3a47-4cbe-a69c-93b6969bdddb" xlink:to="loc_arwr_InitialTransactionPrice_ca62358b-5bfa-4462-8aa8-d5a86300b063" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentEarned_d463bb68-b23d-41a6-a297-8ddad1b47f11" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentEarned"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d4400325-3a47-4cbe-a69c-93b6969bdddb" xlink:to="loc_arwr_MilestonePaymentEarned_d463bb68-b23d-41a6-a297-8ddad1b47f11" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsTakedaPharmaceuticalCompanyLimitedDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#CollaborationandLicenseAgreementsTakedaPharmaceuticalCompanyLimitedDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsTakedaPharmaceuticalCompanyLimitedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5748724b-f312-4f2f-af23-32692a057fc7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5748724b-f312-4f2f-af23-32692a057fc7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_7a47f542-3743-460b-a7f6-d2615138c7c2" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5748724b-f312-4f2f-af23-32692a057fc7" xlink:to="loc_srt_CounterpartyNameAxis_7a47f542-3743-460b-a7f6-d2615138c7c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7a47f542-3743-460b-a7f6-d2615138c7c2_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_7a47f542-3743-460b-a7f6-d2615138c7c2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7a47f542-3743-460b-a7f6-d2615138c7c2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_379be402-25b6-4e20-bcc3-f9ee74e43c04" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_7a47f542-3743-460b-a7f6-d2615138c7c2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_379be402-25b6-4e20-bcc3-f9ee74e43c04" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_1d6daf89-9021-4c06-af0a-67a30e811dae" xlink:href="arwr-20231231.xsd#arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_379be402-25b6-4e20-bcc3-f9ee74e43c04" xlink:to="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_1d6daf89-9021-4c06-af0a-67a30e811dae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_3c6a4eb1-cb6d-4a5e-b5ab-cc167efd216f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5748724b-f312-4f2f-af23-32692a057fc7" xlink:to="loc_us-gaap_TypeOfArrangementAxis_3c6a4eb1-cb6d-4a5e-b5ab-cc167efd216f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_3c6a4eb1-cb6d-4a5e-b5ab-cc167efd216f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_3c6a4eb1-cb6d-4a5e-b5ab-cc167efd216f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_3c6a4eb1-cb6d-4a5e-b5ab-cc167efd216f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_06bf60e0-fc4b-46a1-b609-77d71a516b5e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_3c6a4eb1-cb6d-4a5e-b5ab-cc167efd216f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_06bf60e0-fc4b-46a1-b609-77d71a516b5e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_LicenseAndCoFundingAgreementMember_8509c1dd-2be1-4b35-989c-bbd923ec1656" xlink:href="arwr-20231231.xsd#arwr_LicenseAndCoFundingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_06bf60e0-fc4b-46a1-b609-77d71a516b5e" xlink:to="loc_arwr_LicenseAndCoFundingAgreementMember_8509c1dd-2be1-4b35-989c-bbd923ec1656" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_4c69286f-d8ac-4357-840a-4778150bbc5e" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5748724b-f312-4f2f-af23-32692a057fc7" xlink:to="loc_srt_RangeAxis_4c69286f-d8ac-4357-840a-4778150bbc5e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_4c69286f-d8ac-4357-840a-4778150bbc5e_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_4c69286f-d8ac-4357-840a-4778150bbc5e" xlink:to="loc_srt_RangeMember_4c69286f-d8ac-4357-840a-4778150bbc5e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_fb5f6327-fc6f-4ed9-bc7e-7e414911b450" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_4c69286f-d8ac-4357-840a-4778150bbc5e" xlink:to="loc_srt_RangeMember_fb5f6327-fc6f-4ed9-bc7e-7e414911b450" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_87cf53f0-e5d4-4219-8338-76f335b61066" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_fb5f6327-fc6f-4ed9-bc7e-7e414911b450" xlink:to="loc_srt_MinimumMember_87cf53f0-e5d4-4219-8338-76f335b61066" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_49da21c2-b6bf-4018-9801-f13325bfbe01" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_fb5f6327-fc6f-4ed9-bc7e-7e414911b450" xlink:to="loc_srt_MaximumMember_49da21c2-b6bf-4018-9801-f13325bfbe01" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_PercentageOfEligibleToReceiveTieredRoyaltiesOnNetSales_b8a89cd1-7634-4a15-9474-b453d6bf114b" xlink:href="arwr-20231231.xsd#arwr_PercentageOfEligibleToReceiveTieredRoyaltiesOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_arwr_PercentageOfEligibleToReceiveTieredRoyaltiesOnNetSales_b8a89cd1-7634-4a15-9474-b453d6bf114b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfDistinctPerformanceObligations_c4f558c9-348b-4028-a0b0-1c04269009ce" xlink:href="arwr-20231231.xsd#arwr_NumberOfDistinctPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_arwr_NumberOfDistinctPerformanceObligations_c4f558c9-348b-4028-a0b0-1c04269009ce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfDistinctBundle_b61ece52-fde3-4518-9471-443fec7edd1c" xlink:href="arwr-20231231.xsd#arwr_NumberOfDistinctBundle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_arwr_NumberOfDistinctBundle_b61ece52-fde3-4518-9471-443fec7edd1c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_827e7277-562f-466f-8df0-46cd17d9fd43" xlink:href="arwr-20231231.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_arwr_InitialTransactionPrice_827e7277-562f-466f-8df0-46cd17d9fd43" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentEarned_a1138802-b0c4-4d1b-8780-2566d9331dbb" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentEarned"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_arwr_MilestonePaymentEarned_a1138802-b0c4-4d1b-8780-2566d9331dbb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_d3d3538e-0673-4010-8ca1-046577f3e1b9" xlink:href="arwr-20231231.xsd#arwr_DevelopmentRegulatoryAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_d3d3538e-0673-4010-8ca1-046577f3e1b9" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_d9d8b457-d20e-48e9-97f9-237fd2208ad4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_d9d8b457-d20e-48e9-97f9-237fd2208ad4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_973062a9-121c-46d5-acd4-4d96702f9105" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_us-gaap_EarningsPerShareDiluted_973062a9-121c-46d5-acd4-4d96702f9105" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_3788eab2-b316-4b31-bdb8-20cd501360c1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_3788eab2-b316-4b31-bdb8-20cd501360c1" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_cf1ce433-5ec8-4ffa-9a22-28a0a863aa3f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d17db7b7-85ea-40e8-b645-8c269c8ec27b" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_cf1ce433-5ec8-4ffa-9a22-28a0a863aa3f" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsAmgenIncDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#CollaborationandLicenseAgreementsAmgenIncDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsAmgenIncDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d811f31f-2b62-4fd7-b346-1075ba599e2b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d811f31f-2b62-4fd7-b346-1075ba599e2b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_4248033b-4952-439a-9d09-9a7cd1b70ead" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d811f31f-2b62-4fd7-b346-1075ba599e2b" xlink:to="loc_srt_CounterpartyNameAxis_4248033b-4952-439a-9d09-9a7cd1b70ead" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4248033b-4952-439a-9d09-9a7cd1b70ead_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_4248033b-4952-439a-9d09-9a7cd1b70ead" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4248033b-4952-439a-9d09-9a7cd1b70ead_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f492f519-4dcf-426d-9b6e-be8985908397" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_4248033b-4952-439a-9d09-9a7cd1b70ead" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f492f519-4dcf-426d-9b6e-be8985908397" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AmgenIncorporatedMember_6e600c8e-6b90-4f96-86c9-9f29675cb117" xlink:href="arwr-20231231.xsd#arwr_AmgenIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f492f519-4dcf-426d-9b6e-be8985908397" xlink:to="loc_arwr_AmgenIncorporatedMember_6e600c8e-6b90-4f96-86c9-9f29675cb117" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_9bf36a75-3f39-4cb9-98d2-5de6322845f0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d811f31f-2b62-4fd7-b346-1075ba599e2b" xlink:to="loc_us-gaap_TypeOfArrangementAxis_9bf36a75-3f39-4cb9-98d2-5de6322845f0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9bf36a75-3f39-4cb9-98d2-5de6322845f0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_9bf36a75-3f39-4cb9-98d2-5de6322845f0" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9bf36a75-3f39-4cb9-98d2-5de6322845f0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_8ff6c244-1278-453d-a356-69eefcb22ca4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_9bf36a75-3f39-4cb9-98d2-5de6322845f0" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_8ff6c244-1278-453d-a356-69eefcb22ca4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OlpasiranAgreementMember_9cd403b4-47e0-4c6e-9844-e6c20a78867c" xlink:href="arwr-20231231.xsd#arwr_OlpasiranAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_8ff6c244-1278-453d-a356-69eefcb22ca4" xlink:to="loc_arwr_OlpasiranAgreementMember_9cd403b4-47e0-4c6e-9844-e6c20a78867c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_b17abfd7-379f-49f7-bd2a-7b560263baa1" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d811f31f-2b62-4fd7-b346-1075ba599e2b" xlink:to="loc_srt_RangeAxis_b17abfd7-379f-49f7-bd2a-7b560263baa1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b17abfd7-379f-49f7-bd2a-7b560263baa1_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_b17abfd7-379f-49f7-bd2a-7b560263baa1" xlink:to="loc_srt_RangeMember_b17abfd7-379f-49f7-bd2a-7b560263baa1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_e4f936f2-ce6e-4fd7-9c9a-36ce8d7bda90" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_b17abfd7-379f-49f7-bd2a-7b560263baa1" xlink:to="loc_srt_RangeMember_e4f936f2-ce6e-4fd7-9c9a-36ce8d7bda90" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_8ce3b196-de91-4e08-b7a2-7184de1124b5" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_e4f936f2-ce6e-4fd7-9c9a-36ce8d7bda90" xlink:to="loc_srt_MaximumMember_8ce3b196-de91-4e08-b7a2-7184de1124b5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfAgreements_1e76d89d-cbce-4b07-9fe0-359b1597d8f8" xlink:href="arwr-20231231.xsd#arwr_NumberOfAgreements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_arwr_NumberOfAgreements_1e76d89d-cbce-4b07-9fe0-359b1597d8f8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CashReceivedAsDueUnderCollaborationAgreement_50e991cd-8476-45e2-80b0-6a59e2627aea" xlink:href="arwr-20231231.xsd#arwr_CashReceivedAsDueUnderCollaborationAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_arwr_CashReceivedAsDueUnderCollaborationAgreement_50e991cd-8476-45e2-80b0-6a59e2627aea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_1ccd17ec-217b-4142-b1cf-1f20693513e5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_1ccd17ec-217b-4142-b1cf-1f20693513e5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceived_766a3da3-ff09-4517-9ae6-83290ed3b3b6" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentReceived"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_arwr_MilestonePaymentReceived_766a3da3-ff09-4517-9ae6-83290ed3b3b6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerAssetNetCurrent_68e2a966-c5c5-489e-8b3f-4cab1b1d62ea" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerAssetNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_us-gaap_ContractWithCustomerAssetNetCurrent_68e2a966-c5c5-489e-8b3f-4cab1b1d62ea" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_5d9d6506-2f03-4a2b-aab5-4ed74c3f28cd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_5d9d6506-2f03-4a2b-aab5-4ed74c3f28cd" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdditionalRemainingDevelopmentRegulatoryAndSalesMilestonesPayments_bdcfa09f-3347-4813-8e08-509f0d388207" xlink:href="arwr-20231231.xsd#arwr_AdditionalRemainingDevelopmentRegulatoryAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c717c240-d064-499d-9d10-3b883b84cd0d" xlink:to="loc_arwr_AdditionalRemainingDevelopmentRegulatoryAndSalesMilestonesPayments_bdcfa09f-3347-4813-8e08-509f0d388207" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsVisirnaTherapeuticsIncDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#CollaborationandLicenseAgreementsVisirnaTherapeuticsIncDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsVisirnaTherapeuticsIncDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9af96dc3-561b-4c75-84cf-fcf74669414d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_29138377-d66a-4dfe-aeb3-17a902ea5cfb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9af96dc3-561b-4c75-84cf-fcf74669414d" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_29138377-d66a-4dfe-aeb3-17a902ea5cfb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_c50639a6-2d20-45a9-9940-f085b9aa9ba0" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_29138377-d66a-4dfe-aeb3-17a902ea5cfb" xlink:to="loc_srt_CounterpartyNameAxis_c50639a6-2d20-45a9-9940-f085b9aa9ba0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_c50639a6-2d20-45a9-9940-f085b9aa9ba0_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_c50639a6-2d20-45a9-9940-f085b9aa9ba0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_c50639a6-2d20-45a9-9940-f085b9aa9ba0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e8d8d57e-fd11-4279-b1d8-45e15b1bd4f4" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_c50639a6-2d20-45a9-9940-f085b9aa9ba0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e8d8d57e-fd11-4279-b1d8-45e15b1bd4f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_VisirnaTherapeuticsIncMember_31c10773-7940-4d6b-a1d1-133b4e35bf2f" xlink:href="arwr-20231231.xsd#arwr_VisirnaTherapeuticsIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e8d8d57e-fd11-4279-b1d8-45e15b1bd4f4" xlink:to="loc_arwr_VisirnaTherapeuticsIncMember_31c10773-7940-4d6b-a1d1-133b4e35bf2f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_7d45e83f-ac15-4a4d-bb24-0dadb7d9f0d7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_29138377-d66a-4dfe-aeb3-17a902ea5cfb" xlink:to="loc_us-gaap_TypeOfArrangementAxis_7d45e83f-ac15-4a4d-bb24-0dadb7d9f0d7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7d45e83f-ac15-4a4d-bb24-0dadb7d9f0d7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_7d45e83f-ac15-4a4d-bb24-0dadb7d9f0d7" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7d45e83f-ac15-4a4d-bb24-0dadb7d9f0d7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_71ced55e-78fa-4f45-92a1-c3371e01eae4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_7d45e83f-ac15-4a4d-bb24-0dadb7d9f0d7" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_71ced55e-78fa-4f45-92a1-c3371e01eae4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_VisirnaLicenseAgreementMember_53246564-6ba3-4a6f-86e5-d3d98e676865" xlink:href="arwr-20231231.xsd#arwr_VisirnaLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_71ced55e-78fa-4f45-92a1-c3371e01eae4" xlink:to="loc_arwr_VisirnaLicenseAgreementMember_53246564-6ba3-4a6f-86e5-d3d98e676865" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_e7733334-5eb2-47a1-ac73-4c5ca1dc3de8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9af96dc3-561b-4c75-84cf-fcf74669414d" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_e7733334-5eb2-47a1-ac73-4c5ca1dc3de8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerAssetNetCurrent_4ba435dc-877c-4d47-8d3e-7dcffb550790" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerAssetNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9af96dc3-561b-4c75-84cf-fcf74669414d" xlink:to="loc_us-gaap_ContractWithCustomerAssetNetCurrent_4ba435dc-877c-4d47-8d3e-7dcffb550790" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_603e647c-ed8c-4926-9679-e642ab6b55a1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9af96dc3-561b-4c75-84cf-fcf74669414d" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_603e647c-ed8c-4926-9679-e642ab6b55a1" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/BalanceSheetAccountsSummaryofPropertyandEquipmentDetail" xlink:type="simple" xlink:href="arwr-20231231.xsd#BalanceSheetAccountsSummaryofPropertyandEquipmentDetail"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/BalanceSheetAccountsSummaryofPropertyandEquipmentDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_72a37afb-c6c0-4114-bd29-b2d99edfdc27" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_fb721a2a-c7bd-4c32-895b-2aead400da03" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_72a37afb-c6c0-4114-bd29-b2d99edfdc27" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_fb721a2a-c7bd-4c32-895b-2aead400da03" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_458fe769-9118-481c-91d3-c5251d8d7915" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_fb721a2a-c7bd-4c32-895b-2aead400da03" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_458fe769-9118-481c-91d3-c5251d8d7915" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_458fe769-9118-481c-91d3-c5251d8d7915_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_458fe769-9118-481c-91d3-c5251d8d7915" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_458fe769-9118-481c-91d3-c5251d8d7915_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_458fe769-9118-481c-91d3-c5251d8d7915" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandMember_2f58bc8f-c16c-4fff-b36f-03f068badca9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LandMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:to="loc_us-gaap_LandMember_2f58bc8f-c16c-4fff-b36f-03f068badca9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BuildingMember_0a3dffc1-daf7-4045-b66a-d5afbd55a9da" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BuildingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:to="loc_us-gaap_BuildingMember_0a3dffc1-daf7-4045-b66a-d5afbd55a9da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ResearchEquipmentMember_885da443-f3d4-47e9-825c-49feef6823ec" xlink:href="arwr-20231231.xsd#arwr_ResearchEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:to="loc_arwr_ResearchEquipmentMember_885da443-f3d4-47e9-825c-49feef6823ec" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_473cdf6f-b803-4570-bf49-6df07c8d40a5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_473cdf6f-b803-4570-bf49-6df07c8d40a5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ComputerAndSoftwareMember_6649a409-12a6-482f-9e31-72e9005da216" xlink:href="arwr-20231231.xsd#arwr_ComputerAndSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:to="loc_arwr_ComputerAndSoftwareMember_6649a409-12a6-482f-9e31-72e9005da216" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_2ab0cff6-ba53-423a-909d-43331223a929" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_2ab0cff6-ba53-423a-909d-43331223a929" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConstructionInProgressMember_48bae3e1-9510-4d52-b297-4cfe53acbdc7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConstructionInProgressMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ea0c7c50-6080-4db0-b9df-483f7a702f67" xlink:to="loc_us-gaap_ConstructionInProgressMember_48bae3e1-9510-4d52-b297-4cfe53acbdc7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_dfbdcd0e-aaa1-484f-bd97-1a0249eee9b9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_72a37afb-c6c0-4114-bd29-b2d99edfdc27" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_dfbdcd0e-aaa1-484f-bd97-1a0249eee9b9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_fa0fbe4b-02da-484d-a597-caf48ee2ae2f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_72a37afb-c6c0-4114-bd29-b2d99edfdc27" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_fa0fbe4b-02da-484d-a597-caf48ee2ae2f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_ea1e3338-1275-42f9-921f-5a4f047cd8bb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_72a37afb-c6c0-4114-bd29-b2d99edfdc27" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_ea1e3338-1275-42f9-921f-5a4f047cd8bb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_3bf57a5d-96a1-4e24-9bab-d5cd3fc58fca" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_72a37afb-c6c0-4114-bd29-b2d99edfdc27" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_3bf57a5d-96a1-4e24-9bab-d5cd3fc58fca" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_7c60decf-c903-470b-a79e-97c34646eb10" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_72a37afb-c6c0-4114-bd29-b2d99edfdc27" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_7c60decf-c903-470b-a79e-97c34646eb10" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/InvestmentsSummaryofShorttermLongtermInvestmentsandMarketableSecuritiesDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#InvestmentsSummaryofShorttermLongtermInvestmentsandMarketableSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/InvestmentsSummaryofShorttermLongtermInvestmentsandMarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_920c0195-d287-4568-9e3b-89e78bddf711" xlink:href="arwr-20231231.xsd#arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable_fdfa879b-4f5a-4262-a0a1-6b7758d14165" xlink:href="arwr-20231231.xsd#arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_920c0195-d287-4568-9e3b-89e78bddf711" xlink:to="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable_fdfa879b-4f5a-4262-a0a1-6b7758d14165" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_16f863a8-f4c3-4522-a767-120ce36112ff" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable_fdfa879b-4f5a-4262-a0a1-6b7758d14165" xlink:to="loc_us-gaap_FinancialInstrumentAxis_16f863a8-f4c3-4522-a767-120ce36112ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_16f863a8-f4c3-4522-a767-120ce36112ff_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_16f863a8-f4c3-4522-a767-120ce36112ff" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_16f863a8-f4c3-4522-a767-120ce36112ff_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1f4f0599-4865-4aac-b2cd-a8a7a66b0105" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_16f863a8-f4c3-4522-a767-120ce36112ff" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1f4f0599-4865-4aac-b2cd-a8a7a66b0105" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesMember_0b644dff-c7d3-4a5d-b894-82fdcc3f5ce3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1f4f0599-4865-4aac-b2cd-a8a7a66b0105" xlink:to="loc_us-gaap_DebtSecuritiesMember_0b644dff-c7d3-4a5d-b894-82fdcc3f5ce3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_db621d0b-3b7b-42d3-80b2-19f3b7187419" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_920c0195-d287-4568-9e3b-89e78bddf711" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_db621d0b-3b7b-42d3-80b2-19f3b7187419" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrent_dad00de4-0df6-40c1-88a6-43f3d62dd7a1" xlink:href="arwr-20231231.xsd#arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_920c0195-d287-4568-9e3b-89e78bddf711" xlink:to="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrent_dad00de4-0df6-40c1-88a6-43f3d62dd7a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrent_25218df3-705e-4dc3-b523-4246884e40d8" xlink:href="arwr-20231231.xsd#arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_920c0195-d287-4568-9e3b-89e78bddf711" xlink:to="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrent_25218df3-705e-4dc3-b523-4246884e40d8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_bd0b260f-75db-459e-85e2-1ed41dde8e40" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_920c0195-d287-4568-9e3b-89e78bddf711" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_bd0b260f-75db-459e-85e2-1ed41dde8e40" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/IntangibleAssetsScheduleofIntangibleAssetsDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#IntangibleAssetsScheduleofIntangibleAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/IntangibleAssetsScheduleofIntangibleAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_2d07a0a3-6195-4a7e-bded-9c4f4fccf2b1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_fc8bf4af-fc68-4484-b7b6-bdad8eff0859" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_2d07a0a3-6195-4a7e-bded-9c4f4fccf2b1" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_fc8bf4af-fc68-4484-b7b6-bdad8eff0859" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_bf7dc2d4-b72c-409d-87c6-d095f1337466" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_fc8bf4af-fc68-4484-b7b6-bdad8eff0859" xlink:to="loc_us-gaap_AssetAcquisitionAxis_bf7dc2d4-b72c-409d-87c6-d095f1337466" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_bf7dc2d4-b72c-409d-87c6-d095f1337466_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_bf7dc2d4-b72c-409d-87c6-d095f1337466" xlink:to="loc_us-gaap_AssetAcquisitionDomain_bf7dc2d4-b72c-409d-87c6-d095f1337466_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_bc22cbe0-e776-4f32-8f23-59b867bd81dd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_bf7dc2d4-b72c-409d-87c6-d095f1337466" xlink:to="loc_us-gaap_AssetAcquisitionDomain_bc22cbe0-e776-4f32-8f23-59b867bd81dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NovartisMember_b7c58d78-75c0-4715-815c-4b1d9cef9abe" xlink:href="arwr-20231231.xsd#arwr_NovartisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_bc22cbe0-e776-4f32-8f23-59b867bd81dd" xlink:to="loc_arwr_NovartisMember_b7c58d78-75c0-4715-815c-4b1d9cef9abe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4303da67-499c-4291-bc55-4fbc4433be8b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_fc8bf4af-fc68-4484-b7b6-bdad8eff0859" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4303da67-499c-4291-bc55-4fbc4433be8b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_4303da67-499c-4291-bc55-4fbc4433be8b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4303da67-499c-4291-bc55-4fbc4433be8b" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_4303da67-499c-4291-bc55-4fbc4433be8b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_a0634f2a-4033-4c3a-ab7b-9ecf807e3f02" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_4303da67-499c-4291-bc55-4fbc4433be8b" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_a0634f2a-4033-4c3a-ab7b-9ecf807e3f02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PatentsMember_9042f314-8ced-4799-8e02-947e2282fac6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PatentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_a0634f2a-4033-4c3a-ab7b-9ecf807e3f02" xlink:to="loc_us-gaap_PatentsMember_9042f314-8ced-4799-8e02-947e2282fac6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicensingAgreementsMember_e0391e02-8725-48eb-a20d-8944221ed291" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LicensingAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_a0634f2a-4033-4c3a-ab7b-9ecf807e3f02" xlink:to="loc_us-gaap_LicensingAgreementsMember_e0391e02-8725-48eb-a20d-8944221ed291" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_7846c879-8c54-49e7-9467-5e86abd61ad6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_2d07a0a3-6195-4a7e-bded-9c4f4fccf2b1" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_7846c879-8c54-49e7-9467-5e86abd61ad6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_8e682f56-94c1-47a8-985e-3426d274991c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_2d07a0a3-6195-4a7e-bded-9c4f4fccf2b1" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_8e682f56-94c1-47a8-985e-3426d274991c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FiniteLivedIntangibleAssetsImpairment_c71642b6-cf92-44a7-adfd-f61ca70f45a3" xlink:href="arwr-20231231.xsd#arwr_FiniteLivedIntangibleAssetsImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_2d07a0a3-6195-4a7e-bded-9c4f4fccf2b1" xlink:to="loc_arwr_FiniteLivedIntangibleAssetsImpairment_c71642b6-cf92-44a7-adfd-f61ca70f45a3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_7f2681b6-e8c4-4a43-a06c-9ab72de088b8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_2d07a0a3-6195-4a7e-bded-9c4f4fccf2b1" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_7f2681b6-e8c4-4a43-a06c-9ab72de088b8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_baee7b58-5df0-4e5c-a40e-68b900f2bf6b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_2d07a0a3-6195-4a7e-bded-9c4f4fccf2b1" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_baee7b58-5df0-4e5c-a40e-68b900f2bf6b" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockholdersEquityDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#StockholdersEquityDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockholdersEquityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_7b144526-d15b-4567-b1fd-f454219ea475" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_7b144526-d15b-4567-b1fd-f454219ea475" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_1cd9072b-d741-4e37-a5ed-568309aaa386" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_7b144526-d15b-4567-b1fd-f454219ea475" xlink:to="loc_us-gaap_PlanNameAxis_1cd9072b-d741-4e37-a5ed-568309aaa386" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_1cd9072b-d741-4e37-a5ed-568309aaa386_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_1cd9072b-d741-4e37-a5ed-568309aaa386" xlink:to="loc_us-gaap_PlanNameDomain_1cd9072b-d741-4e37-a5ed-568309aaa386_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_6f62fc9f-a06c-4e86-badc-b4715b99e56c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_1cd9072b-d741-4e37-a5ed-568309aaa386" xlink:to="loc_us-gaap_PlanNameDomain_6f62fc9f-a06c-4e86-badc-b4715b99e56c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandFourEquityIncentivePlanTwoThousandThirteenEquityIncentivePlanTwoThousandTwentyOneEquityIncentivePlanAndInducementGrantsMember_c445d36c-dbfd-44a8-99fd-f21525bfeb5d" xlink:href="arwr-20231231.xsd#arwr_TwoThousandFourEquityIncentivePlanTwoThousandThirteenEquityIncentivePlanTwoThousandTwentyOneEquityIncentivePlanAndInducementGrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_6f62fc9f-a06c-4e86-badc-b4715b99e56c" xlink:to="loc_arwr_TwoThousandFourEquityIncentivePlanTwoThousandThirteenEquityIncentivePlanTwoThousandTwentyOneEquityIncentivePlanAndInducementGrantsMember_c445d36c-dbfd-44a8-99fd-f21525bfeb5d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_ced8a13f-dce5-41f6-8b41-572dc1c8967a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_7b144526-d15b-4567-b1fd-f454219ea475" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_ced8a13f-dce5-41f6-8b41-572dc1c8967a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_ced8a13f-dce5-41f6-8b41-572dc1c8967a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_ced8a13f-dce5-41f6-8b41-572dc1c8967a" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_ced8a13f-dce5-41f6-8b41-572dc1c8967a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_85970177-66e7-4e20-8fd1-bfd28c4b5777" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_ced8a13f-dce5-41f6-8b41-572dc1c8967a" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_85970177-66e7-4e20-8fd1-bfd28c4b5777" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_UnderwritingAgreementMember_6a281518-e7fc-42a7-a7df-e843e977f53e" xlink:href="arwr-20231231.xsd#arwr_UnderwritingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_85970177-66e7-4e20-8fd1-bfd28c4b5777" xlink:to="loc_arwr_UnderwritingAgreementMember_6a281518-e7fc-42a7-a7df-e843e977f53e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AtTheMarketAgreementMember_de6ddfc9-25a1-46cc-ac34-05b0ed881763" xlink:href="arwr-20231231.xsd#arwr_AtTheMarketAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_85970177-66e7-4e20-8fd1-bfd28c4b5777" xlink:to="loc_arwr_AtTheMarketAgreementMember_de6ddfc9-25a1-46cc-ac34-05b0ed881763" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_9b9b4fdd-beea-4e4d-a324-aa2134ab4aa9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_7b144526-d15b-4567-b1fd-f454219ea475" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_9b9b4fdd-beea-4e4d-a324-aa2134ab4aa9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_9b9b4fdd-beea-4e4d-a324-aa2134ab4aa9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_9b9b4fdd-beea-4e4d-a324-aa2134ab4aa9" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_9b9b4fdd-beea-4e4d-a324-aa2134ab4aa9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_583e6c87-294f-4ed7-b2f3-8700303dd9c6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_9b9b4fdd-beea-4e4d-a324-aa2134ab4aa9" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_583e6c87-294f-4ed7-b2f3-8700303dd9c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_ce584074-ac17-444f-9a90-193d0a1af560" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_583e6c87-294f-4ed7-b2f3-8700303dd9c6" xlink:to="loc_us-gaap_SubsequentEventMember_ce584074-ac17-444f-9a90-193d0a1af560" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_9ee626b9-546a-4631-8200-68f7d89126f8" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_7b144526-d15b-4567-b1fd-f454219ea475" xlink:to="loc_srt_RangeAxis_9ee626b9-546a-4631-8200-68f7d89126f8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_9ee626b9-546a-4631-8200-68f7d89126f8_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_9ee626b9-546a-4631-8200-68f7d89126f8" xlink:to="loc_srt_RangeMember_9ee626b9-546a-4631-8200-68f7d89126f8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2e369395-9388-428e-96c2-640669c2a467" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_9ee626b9-546a-4631-8200-68f7d89126f8" xlink:to="loc_srt_RangeMember_2e369395-9388-428e-96c2-640669c2a467" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_48131387-26ca-4838-9279-7fec24e967c8" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_2e369395-9388-428e-96c2-640669c2a467" xlink:to="loc_srt_MaximumMember_48131387-26ca-4838-9279-7fec24e967c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_278e6b76-1b8b-4cab-b3f9-667fd73f681f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_278e6b76-1b8b-4cab-b3f9-667fd73f681f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_582eca6d-7016-496d-a790-c8041e10540f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_582eca6d-7016-496d-a790-c8041e10540f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesIssued_5926f2f9-8e91-4772-8240-d93cb0c88d25" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_CommonStockSharesIssued_5926f2f9-8e91-4772-8240-d93cb0c88d25" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_e5854c86-5585-4a2d-9d36-529182b853ee" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_e5854c86-5585-4a2d-9d36-529182b853ee" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_98cd25e2-500d-4ad7-9080-ba0fb34dc782" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_98cd25e2-500d-4ad7-9080-ba0fb34dc782" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesAuthorized_00ec257a-d004-4d48-b9b1-4ad90b1739a8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_PreferredStockSharesAuthorized_00ec257a-d004-4d48-b9b1-4ad90b1739a8" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesIssued_d19f769f-9d70-4a14-af81-6a22f15aac72" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_PreferredStockSharesIssued_d19f769f-9d70-4a14-af81-6a22f15aac72" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_ff032cb0-082c-4c76-8a6d-07d8da1c02ca" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_ff032cb0-082c-4c76-8a6d-07d8da1c02ca" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_06a01550-a248-45c3-b6d6-e99537f57299" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_06a01550-a248-45c3-b6d6-e99537f57299" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_b75fcc98-1efc-4481-9a83-ad4e8887c12d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_b75fcc98-1efc-4481-9a83-ad4e8887c12d" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_f7af656f-2519-4c52-b0da-a8c671d0018e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_f7af656f-2519-4c52-b0da-a8c671d0018e" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SaleOfStockAggregatePurchasePrice_1e8e6986-00bf-4a00-b4af-7ee3e599f0a7" xlink:href="arwr-20231231.xsd#arwr_SaleOfStockAggregatePurchasePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_arwr_SaleOfStockAggregatePurchasePrice_1e8e6986-00bf-4a00-b4af-7ee3e599f0a7" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_53c70433-8eb8-493c-b71d-fae8b352fa90" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_53c70433-8eb8-493c-b71d-fae8b352fa90" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommonStockCapitalSharesValueReservedForFutureIssuance_6b314190-f412-422a-8722-5a8723233280" xlink:href="arwr-20231231.xsd#arwr_CommonStockCapitalSharesValueReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_arwr_CommonStockCapitalSharesValueReservedForFutureIssuance_6b314190-f412-422a-8722-5a8723233280" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_PercentageOfCommissionOnAggregateGrossProceedsFromSaleOfCommonStock_93851208-aa8c-4f72-b3d0-add9ff586f35" xlink:href="arwr-20231231.xsd#arwr_PercentageOfCommissionOnAggregateGrossProceedsFromSaleOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_arwr_PercentageOfCommissionOnAggregateGrossProceedsFromSaleOfCommonStock_93851208-aa8c-4f72-b3d0-add9ff586f35" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_f9f3cf55-4324-478c-9c15-b2ed7b591ad3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_ceb67dd6-342e-441b-b152-2d9f935ab24b" xlink:to="loc_us-gaap_SharesIssued_f9f3cf55-4324-478c-9c15-b2ed7b591ad3" xlink:type="arc" order="15"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CommitmentsandContingenciesAdditionalInformationDetail" xlink:type="simple" xlink:href="arwr-20231231.xsd#CommitmentsandContingenciesAdditionalInformationDetail"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CommitmentsandContingenciesAdditionalInformationDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsLineItems_2d9a4a38-3449-4a53-b1eb-e33bca5a606d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherCommitmentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsTable_bc9b1b11-a997-4158-9e11-fab9387cb479" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherCommitmentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_2d9a4a38-3449-4a53-b1eb-e33bca5a606d" xlink:to="loc_us-gaap_OtherCommitmentsTable_bc9b1b11-a997-4158-9e11-fab9387cb479" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_2cf42573-89b2-488b-a119-94875c3920af" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OtherCommitmentsTable_bc9b1b11-a997-4158-9e11-fab9387cb479" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_2cf42573-89b2-488b-a119-94875c3920af" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_2cf42573-89b2-488b-a119-94875c3920af_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_2cf42573-89b2-488b-a119-94875c3920af" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_2cf42573-89b2-488b-a119-94875c3920af_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4084c486-5dac-4ea3-a889-6a358c9aafe8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_2cf42573-89b2-488b-a119-94875c3920af" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4084c486-5dac-4ea3-a889-6a358c9aafe8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DrugManufacturingFacilityMember_5af6d0e8-14eb-4786-88d0-2868e6d2f4c4" xlink:href="arwr-20231231.xsd#arwr_DrugManufacturingFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4084c486-5dac-4ea3-a889-6a358c9aafe8" xlink:to="loc_arwr_DrugManufacturingFacilityMember_5af6d0e8-14eb-4786-88d0-2868e6d2f4c4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_LaboratoryAndOfficeFacilityMember_f9b62c2c-754a-4f4c-9b07-23e62e8a1f26" xlink:href="arwr-20231231.xsd#arwr_LaboratoryAndOfficeFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4084c486-5dac-4ea3-a889-6a358c9aafe8" xlink:to="loc_arwr_LaboratoryAndOfficeFacilityMember_f9b62c2c-754a-4f4c-9b07-23e62e8a1f26" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FacilitiesMember_f5b99a26-c23d-4c4f-8cd7-dfaa6e1a8681" xlink:href="arwr-20231231.xsd#arwr_FacilitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4084c486-5dac-4ea3-a889-6a358c9aafe8" xlink:to="loc_arwr_FacilitiesMember_f5b99a26-c23d-4c4f-8cd7-dfaa6e1a8681" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_14ff863e-36cd-45d5-b13b-b4a3c1413528" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OtherCommitmentsTable_bc9b1b11-a997-4158-9e11-fab9387cb479" xlink:to="loc_srt_StatementGeographicalAxis_14ff863e-36cd-45d5-b13b-b4a3c1413528" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_14ff863e-36cd-45d5-b13b-b4a3c1413528_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_14ff863e-36cd-45d5-b13b-b4a3c1413528" xlink:to="loc_srt_SegmentGeographicalDomain_14ff863e-36cd-45d5-b13b-b4a3c1413528_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_443b2d47-ef30-46a7-8973-0bf40ebdfb98" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_14ff863e-36cd-45d5-b13b-b4a3c1413528" xlink:to="loc_srt_SegmentGeographicalDomain_443b2d47-ef30-46a7-8973-0bf40ebdfb98" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_stpr_WI_ce44f905-e3e8-4c5f-b64d-be1d5344db51" xlink:href="https://xbrl.sec.gov/stpr/2023/stpr-2023.xsd#stpr_WI"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_443b2d47-ef30-46a7-8973-0bf40ebdfb98" xlink:to="loc_stpr_WI_ce44f905-e3e8-4c5f-b64d-be1d5344db51" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_fb80998a-3c69-4aa8-b3e2-558f6d216566" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OtherCommitmentsTable_bc9b1b11-a997-4158-9e11-fab9387cb479" xlink:to="loc_srt_RangeAxis_fb80998a-3c69-4aa8-b3e2-558f6d216566" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_fb80998a-3c69-4aa8-b3e2-558f6d216566_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_fb80998a-3c69-4aa8-b3e2-558f6d216566" xlink:to="loc_srt_RangeMember_fb80998a-3c69-4aa8-b3e2-558f6d216566_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_49880f09-bba9-4cd4-b411-70accd259eec" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_fb80998a-3c69-4aa8-b3e2-558f6d216566" xlink:to="loc_srt_RangeMember_49880f09-bba9-4cd4-b411-70accd259eec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_40e85372-5cc1-481e-a405-543cfcc33e22" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_49880f09-bba9-4cd4-b411-70accd259eec" xlink:to="loc_srt_MinimumMember_40e85372-5cc1-481e-a405-543cfcc33e22" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_9a5215d4-dc15-4ed3-a57c-85f76eec2af2" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_49880f09-bba9-4cd4-b411-70accd259eec" xlink:to="loc_srt_MaximumMember_9a5215d4-dc15-4ed3-a57c-85f76eec2af2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingencyAccrualAtCarryingValue_c655b128-0b32-40f5-83d4-b10a53f44022" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LossContingencyAccrualAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_2d9a4a38-3449-4a53-b1eb-e33bca5a606d" xlink:to="loc_us-gaap_LossContingencyAccrualAtCarryingValue_c655b128-0b32-40f5-83d4-b10a53f44022" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AreaOfLand_0ee6cc12-0cf0-4d71-92f9-9fb2e30281ba" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AreaOfLand"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_2d9a4a38-3449-4a53-b1eb-e33bca5a606d" xlink:to="loc_us-gaap_AreaOfLand_0ee6cc12-0cf0-4d71-92f9-9fb2e30281ba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommitmentsCapitalExpendituresIncurredToDate_e1f30155-a1bc-406f-968a-732027f05e07" xlink:href="arwr-20231231.xsd#arwr_CommitmentsCapitalExpendituresIncurredToDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_2d9a4a38-3449-4a53-b1eb-e33bca5a606d" xlink:to="loc_arwr_CommitmentsCapitalExpendituresIncurredToDate_e1f30155-a1bc-406f-968a-732027f05e07" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AmountIntendsToInvestForBuildoutOfFacilities_dd688684-a10d-48b6-bfde-c79ca515f49a" xlink:href="arwr-20231231.xsd#arwr_AmountIntendsToInvestForBuildoutOfFacilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_2d9a4a38-3449-4a53-b1eb-e33bca5a606d" xlink:to="loc_arwr_AmountIntendsToInvestForBuildoutOfFacilities_dd688684-a10d-48b6-bfde-c79ca515f49a" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/LeasesNarrativeDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#LeasesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/LeasesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_447487f4-0833-4bf7-93ad-14296d048895" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_447487f4-0833-4bf7-93ad-14296d048895" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_6630da1f-40f0-4704-b2e2-fc1edee6d4db" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_447487f4-0833-4bf7-93ad-14296d048895" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_6630da1f-40f0-4704-b2e2-fc1edee6d4db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_6630da1f-40f0-4704-b2e2-fc1edee6d4db_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_6630da1f-40f0-4704-b2e2-fc1edee6d4db" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_6630da1f-40f0-4704-b2e2-fc1edee6d4db_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_3bd0eaab-d8f2-4e90-85a4-20618dcbfed5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_6630da1f-40f0-4704-b2e2-fc1edee6d4db" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_3bd0eaab-d8f2-4e90-85a4-20618dcbfed5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CorporateHeadquartersInPasadenaMember_9fa5f538-4dca-4c06-983d-c28d8c768b4c" xlink:href="arwr-20231231.xsd#arwr_CorporateHeadquartersInPasadenaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_3bd0eaab-d8f2-4e90-85a4-20618dcbfed5" xlink:to="loc_arwr_CorporateHeadquartersInPasadenaMember_9fa5f538-4dca-4c06-983d-c28d8c768b4c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ResearchFacilityInSanDiegoMember_277a0f84-0bbe-4afd-9a74-4fd7d0df3b18" xlink:href="arwr-20231231.xsd#arwr_ResearchFacilityInSanDiegoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_3bd0eaab-d8f2-4e90-85a4-20618dcbfed5" xlink:to="loc_arwr_ResearchFacilityInSanDiegoMember_277a0f84-0bbe-4afd-9a74-4fd7d0df3b18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ResearchFacilityInMadisonMember_3bac86e8-e116-4584-bb78-cbaafcb5f176" xlink:href="arwr-20231231.xsd#arwr_ResearchFacilityInMadisonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_3bd0eaab-d8f2-4e90-85a4-20618dcbfed5" xlink:to="loc_arwr_ResearchFacilityInMadisonMember_3bac86e8-e116-4584-bb78-cbaafcb5f176" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_15830d59-e340-4531-b600-dfa1a1fb1b9e" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_447487f4-0833-4bf7-93ad-14296d048895" xlink:to="loc_srt_StatementGeographicalAxis_15830d59-e340-4531-b600-dfa1a1fb1b9e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_15830d59-e340-4531-b600-dfa1a1fb1b9e_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_15830d59-e340-4531-b600-dfa1a1fb1b9e" xlink:to="loc_srt_SegmentGeographicalDomain_15830d59-e340-4531-b600-dfa1a1fb1b9e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_535a245e-43d7-4947-9c00-83ab3ab9b1d5" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_15830d59-e340-4531-b600-dfa1a1fb1b9e" xlink:to="loc_srt_SegmentGeographicalDomain_535a245e-43d7-4947-9c00-83ab3ab9b1d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_stpr_CA_546387ae-70eb-4591-8269-bf00a348e9b0" xlink:href="https://xbrl.sec.gov/stpr/2023/stpr-2023.xsd#stpr_CA"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_535a245e-43d7-4947-9c00-83ab3ab9b1d5" xlink:to="loc_stpr_CA_546387ae-70eb-4591-8269-bf00a348e9b0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_stpr_WI_4dc401b8-e34f-4acd-b74e-00d7fb14a13d" xlink:href="https://xbrl.sec.gov/stpr/2023/stpr-2023.xsd#stpr_WI"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_535a245e-43d7-4947-9c00-83ab3ab9b1d5" xlink:to="loc_stpr_WI_4dc401b8-e34f-4acd-b74e-00d7fb14a13d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_275aa4b1-1b22-4d3a-940f-b3c06d087a71" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_447487f4-0833-4bf7-93ad-14296d048895" xlink:to="loc_srt_CounterpartyNameAxis_275aa4b1-1b22-4d3a-940f-b3c06d087a71" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_275aa4b1-1b22-4d3a-940f-b3c06d087a71_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_275aa4b1-1b22-4d3a-940f-b3c06d087a71" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_275aa4b1-1b22-4d3a-940f-b3c06d087a71_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d61f19bb-854c-4553-ab70-ec47c7d74076" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_275aa4b1-1b22-4d3a-940f-b3c06d087a71" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d61f19bb-854c-4553-ab70-ec47c7d74076" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ColoradoOwnerLLCMember_e4341026-cbee-4c21-b910-4b73889e55c8" xlink:href="arwr-20231231.xsd#arwr_ColoradoOwnerLLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d61f19bb-854c-4553-ab70-ec47c7d74076" xlink:to="loc_arwr_ColoradoOwnerLLCMember_e4341026-cbee-4c21-b910-4b73889e55c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_26f39e9e-2e22-4d3a-9d16-f5bd60af4e95" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_447487f4-0833-4bf7-93ad-14296d048895" xlink:to="loc_srt_RangeAxis_26f39e9e-2e22-4d3a-9d16-f5bd60af4e95" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_26f39e9e-2e22-4d3a-9d16-f5bd60af4e95_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_26f39e9e-2e22-4d3a-9d16-f5bd60af4e95" xlink:to="loc_srt_RangeMember_26f39e9e-2e22-4d3a-9d16-f5bd60af4e95_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_37437bfd-8d17-44e4-8b86-85f206c95882" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_26f39e9e-2e22-4d3a-9d16-f5bd60af4e95" xlink:to="loc_srt_RangeMember_37437bfd-8d17-44e4-8b86-85f206c95882" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_5cf3d060-f0bb-48f9-a7bd-fc6834f2b391" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_37437bfd-8d17-44e4-8b86-85f206c95882" xlink:to="loc_srt_MaximumMember_5cf3d060-f0bb-48f9-a7bd-fc6834f2b391" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandSubjectToGroundLeases_a226f8de-e702-4319-8203-6dbeb59050c8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LandSubjectToGroundLeases"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_us-gaap_LandSubjectToGroundLeases_a226f8de-e702-4319-8203-6dbeb59050c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfOptionsToRenew_ba41f810-2656-48ec-8b77-929aa6215ab3" xlink:href="arwr-20231231.xsd#arwr_NumberOfOptionsToRenew"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_arwr_NumberOfOptionsToRenew_ba41f810-2656-48ec-8b77-929aa6215ab3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_f3ee6655-dac7-454d-8b5f-b56ed9c23cd7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_f3ee6655-dac7-454d-8b5f-b56ed9c23cd7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseTermOfContract_a0f8351a-a5e3-4922-a1f2-1dadc0f236b6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LesseeOperatingLeaseTermOfContract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_us-gaap_LesseeOperatingLeaseTermOfContract_a0f8351a-a5e3-4922-a1f2-1dadc0f236b6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MaximumAdditionalTenantImprovementAllowance_24292087-8dd7-4b76-a7cf-cc2f3139b3cc" xlink:href="arwr-20231231.xsd#arwr_MaximumAdditionalTenantImprovementAllowance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_arwr_MaximumAdditionalTenantImprovementAllowance_24292087-8dd7-4b76-a7cf-cc2f3139b3cc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum_b763f62c-2f29-4cfc-9c1e-80ca9e2a0e55" xlink:href="arwr-20231231.xsd#arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum_b763f62c-2f29-4cfc-9c1e-80ca9e2a0e55" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdditionalTenantImprovementAllowanceLiability_b38212eb-b1b7-40bc-a1b8-fe4bdb508d15" xlink:href="arwr-20231231.xsd#arwr_AdditionalTenantImprovementAllowanceLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_arwr_AdditionalTenantImprovementAllowanceLiability_b38212eb-b1b7-40bc-a1b8-fe4bdb508d15" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermLeaseCost_7efa9158-f1ea-4a67-b688-ab108e2990f4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShortTermLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_be5d0ce5-cdf0-4ddd-a277-998f9b661379" xlink:to="loc_us-gaap_ShortTermLeaseCost_7efa9158-f1ea-4a67-b688-ab108e2990f4" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/LeasesComponentsofLeaseAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#LeasesComponentsofLeaseAssetsandLiabilitiesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/LeasesComponentsofLeaseAssetsandLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeasedAssetsLineItems_5e1194f6-bc9e-4eac-86df-dee22b0a2407" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeasedAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfOperatingLeasedAssetsTable_d2c79bbe-7739-4ddf-8dfd-e1aa7ddb00ae" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfOperatingLeasedAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OperatingLeasedAssetsLineItems_5e1194f6-bc9e-4eac-86df-dee22b0a2407" xlink:to="loc_us-gaap_ScheduleOfOperatingLeasedAssetsTable_d2c79bbe-7739-4ddf-8dfd-e1aa7ddb00ae" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_95d1577f-602a-475f-a527-dddee6914928" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfOperatingLeasedAssetsTable_d2c79bbe-7739-4ddf-8dfd-e1aa7ddb00ae" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_95d1577f-602a-475f-a527-dddee6914928" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_95d1577f-602a-475f-a527-dddee6914928_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_95d1577f-602a-475f-a527-dddee6914928" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_95d1577f-602a-475f-a527-dddee6914928_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_9ef3f979-c6c5-4583-982f-a9c01852ebbe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_95d1577f-602a-475f-a527-dddee6914928" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_9ef3f979-c6c5-4583-982f-a9c01852ebbe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_acd0e49f-6954-4043-9768-af09218004c4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_9ef3f979-c6c5-4583-982f-a9c01852ebbe" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_acd0e49f-6954-4043-9768-af09218004c4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_b997213f-a187-45c6-961c-d14ae31dcbef" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_9ef3f979-c6c5-4583-982f-a9c01852ebbe" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_b997213f-a187-45c6-961c-d14ae31dcbef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_b68bd447-2411-4913-939f-e35ff385a82b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsAndLiabilitiesLesseeAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLeasedAssetsLineItems_5e1194f6-bc9e-4eac-86df-dee22b0a2407" xlink:to="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_b68bd447-2411-4913-939f-e35ff385a82b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_c3f7fdc8-6e55-49e8-8c76-76a905dedabf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_b68bd447-2411-4913-939f-e35ff385a82b" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_c3f7fdc8-6e55-49e8-8c76-76a905dedabf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_694b4cfc-e472-4034-989d-692a5e012edf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_b68bd447-2411-4913-939f-e35ff385a82b" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_694b4cfc-e472-4034-989d-692a5e012edf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_e7a61db0-0a35-463b-aac5-5df0343cd7fe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_b68bd447-2411-4913-939f-e35ff385a82b" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_e7a61db0-0a35-463b-aac5-5df0343cd7fe" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseCostAbstract_0e1d06e6-88a9-4a0b-baeb-d44edfaadcb7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LeaseCostAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLeasedAssetsLineItems_5e1194f6-bc9e-4eac-86df-dee22b0a2407" xlink:to="loc_us-gaap_LeaseCostAbstract_0e1d06e6-88a9-4a0b-baeb-d44edfaadcb7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseCost_d3830de2-fbe5-4d26-a878-475d2dfd4964" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseCostAbstract_0e1d06e6-88a9-4a0b-baeb-d44edfaadcb7" xlink:to="loc_us-gaap_OperatingLeaseCost_d3830de2-fbe5-4d26-a878-475d2dfd4964" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableLeaseCost_243c6628-19bb-4792-9fb5-198f6ca4498d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_VariableLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseCostAbstract_0e1d06e6-88a9-4a0b-baeb-d44edfaadcb7" xlink:to="loc_us-gaap_VariableLeaseCost_243c6628-19bb-4792-9fb5-198f6ca4498d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseCost_e118a546-7a68-4ffe-bc89-8b60203297ff" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseCostAbstract_0e1d06e6-88a9-4a0b-baeb-d44edfaadcb7" xlink:to="loc_us-gaap_LeaseCost_e118a546-7a68-4ffe-bc89-8b60203297ff" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationNarrativeDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#StockBasedCompensationNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c7f0bb3a-d35f-4cb2-94ac-15b5d6104c45" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c7f0bb3a-d35f-4cb2-94ac-15b5d6104c45" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_25125133-94a8-4c50-bc29-eb52e06a00b1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c7f0bb3a-d35f-4cb2-94ac-15b5d6104c45" xlink:to="loc_us-gaap_PlanNameAxis_25125133-94a8-4c50-bc29-eb52e06a00b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_25125133-94a8-4c50-bc29-eb52e06a00b1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_25125133-94a8-4c50-bc29-eb52e06a00b1" xlink:to="loc_us-gaap_PlanNameDomain_25125133-94a8-4c50-bc29-eb52e06a00b1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_d0411f32-4b5f-483a-b8c5-c42604014e7f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_25125133-94a8-4c50-bc29-eb52e06a00b1" xlink:to="loc_us-gaap_PlanNameDomain_d0411f32-4b5f-483a-b8c5-c42604014e7f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandsFourEquityIncentivePlanMember_23675b51-603b-4e82-9caa-d2c8314c60cc" xlink:href="arwr-20231231.xsd#arwr_TwoThousandsFourEquityIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d0411f32-4b5f-483a-b8c5-c42604014e7f" xlink:to="loc_arwr_TwoThousandsFourEquityIncentivePlanMember_23675b51-603b-4e82-9caa-d2c8314c60cc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandsThirteenIncentivePlanMember_b57b0651-4a32-43a1-8349-c68f884e3468" xlink:href="arwr-20231231.xsd#arwr_TwoThousandsThirteenIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d0411f32-4b5f-483a-b8c5-c42604014e7f" xlink:to="loc_arwr_TwoThousandsThirteenIncentivePlanMember_b57b0651-4a32-43a1-8349-c68f884e3468" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_46761191-3cec-4f08-adb0-95f344312052" xlink:href="arwr-20231231.xsd#arwr_TwoThousandTwentyOneIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d0411f32-4b5f-483a-b8c5-c42604014e7f" xlink:to="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_46761191-3cec-4f08-adb0-95f344312052" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InducementAwardsMember_e89411a2-ab2b-4bce-abfc-1db9c8f95019" xlink:href="arwr-20231231.xsd#arwr_InducementAwardsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d0411f32-4b5f-483a-b8c5-c42604014e7f" xlink:to="loc_arwr_InducementAwardsMember_e89411a2-ab2b-4bce-abfc-1db9c8f95019" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_VisirnaESOPMember_b8ddd701-bee6-4862-9a2e-1323957c67d5" xlink:href="arwr-20231231.xsd#arwr_VisirnaESOPMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d0411f32-4b5f-483a-b8c5-c42604014e7f" xlink:to="loc_arwr_VisirnaESOPMember_b8ddd701-bee6-4862-9a2e-1323957c67d5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_2d6ba3f5-376b-4bc6-9a05-827cdf17c964" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c7f0bb3a-d35f-4cb2-94ac-15b5d6104c45" xlink:to="loc_us-gaap_AwardTypeAxis_2d6ba3f5-376b-4bc6-9a05-827cdf17c964" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2d6ba3f5-376b-4bc6-9a05-827cdf17c964_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_2d6ba3f5-376b-4bc6-9a05-827cdf17c964" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2d6ba3f5-376b-4bc6-9a05-827cdf17c964_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7c006fda-2535-43b2-aae9-aadcdf134c2c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_2d6ba3f5-376b-4bc6-9a05-827cdf17c964" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7c006fda-2535-43b2-aae9-aadcdf134c2c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_8ab6b774-ca18-4dd5-b17d-79bdb7a50058" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7c006fda-2535-43b2-aae9-aadcdf134c2c" xlink:to="loc_us-gaap_EmployeeStockOptionMember_8ab6b774-ca18-4dd5-b17d-79bdb7a50058" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_50e792aa-286b-4c87-99ac-06be1ee5642b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7c006fda-2535-43b2-aae9-aadcdf134c2c" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_50e792aa-286b-4c87-99ac-06be1ee5642b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_ff0e848d-527e-44bc-ae46-8887a1b85b45" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_ff0e848d-527e-44bc-ae46-8887a1b85b45" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_7052e23f-3e76-4eed-b82b-ad753f18af7e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_7052e23f-3e76-4eed-b82b-ad753f18af7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_f7090f6b-1a1e-4db7-9990-2b2cffa64f20" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_f7090f6b-1a1e-4db7-9990-2b2cffa64f20" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_3b222eb6-2cd1-406d-9143-8937f34fc72a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_3b222eb6-2cd1-406d-9143-8937f34fc72a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_ae0641c3-c357-444e-8550-6d8740e39746" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_ae0641c3-c357-444e-8550-6d8740e39746" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_c8e4475c-75b8-448b-95c6-30e009ae0e25" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_c8e4475c-75b8-448b-95c6-30e009ae0e25" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_b2a322ba-0847-4133-8e96-fa53b9542243" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_b2a322ba-0847-4133-8e96-fa53b9542243" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_84fd5b88-c89b-449c-9fee-7e4e50fb64d9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_84fd5b88-c89b-449c-9fee-7e4e50fb64d9" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_7f50e1ab-9baa-4955-8a12-87451b37b015" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_7f50e1ab-9baa-4955-8a12-87451b37b015" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_763f5136-7b26-4276-bc63-f71471d68381" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49850043-92d4-4d35-aa9c-5f77d55cf85b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_763f5136-7b26-4276-bc63-f71471d68381" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofGrantedandOutstandingSharesDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#StockBasedCompensationSummaryofGrantedandOutstandingSharesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofGrantedandOutstandingSharesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_e21fb069-66a2-4b0a-8544-ea218dda85db" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e6eac579-cd84-4455-908d-6528e9768d4b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_e21fb069-66a2-4b0a-8544-ea218dda85db" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e6eac579-cd84-4455-908d-6528e9768d4b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_849c6d30-df95-4d8d-847b-5c21d604d99d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e6eac579-cd84-4455-908d-6528e9768d4b" xlink:to="loc_us-gaap_PlanNameAxis_849c6d30-df95-4d8d-847b-5c21d604d99d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_849c6d30-df95-4d8d-847b-5c21d604d99d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_849c6d30-df95-4d8d-847b-5c21d604d99d" xlink:to="loc_us-gaap_PlanNameDomain_849c6d30-df95-4d8d-847b-5c21d604d99d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_679d1f07-068f-4d00-8bb4-c4a7cb1c8f75" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_849c6d30-df95-4d8d-847b-5c21d604d99d" xlink:to="loc_us-gaap_PlanNameDomain_679d1f07-068f-4d00-8bb4-c4a7cb1c8f75" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandsFourEquityIncentivePlanMember_09892088-b76a-4e91-9cd5-e8af764bb6a3" xlink:href="arwr-20231231.xsd#arwr_TwoThousandsFourEquityIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_679d1f07-068f-4d00-8bb4-c4a7cb1c8f75" xlink:to="loc_arwr_TwoThousandsFourEquityIncentivePlanMember_09892088-b76a-4e91-9cd5-e8af764bb6a3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandsThirteenIncentivePlanMember_aff84ba4-c927-4023-8efc-37bf893524d5" xlink:href="arwr-20231231.xsd#arwr_TwoThousandsThirteenIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_679d1f07-068f-4d00-8bb4-c4a7cb1c8f75" xlink:to="loc_arwr_TwoThousandsThirteenIncentivePlanMember_aff84ba4-c927-4023-8efc-37bf893524d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_5e9653ef-57d3-42c7-a2c0-49d53e5f2a0d" xlink:href="arwr-20231231.xsd#arwr_TwoThousandTwentyOneIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_679d1f07-068f-4d00-8bb4-c4a7cb1c8f75" xlink:to="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_5e9653ef-57d3-42c7-a2c0-49d53e5f2a0d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InducementAwardsMember_e58d78ed-6a6a-45ab-bdce-47d6ccd18b10" xlink:href="arwr-20231231.xsd#arwr_InducementAwardsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_679d1f07-068f-4d00-8bb4-c4a7cb1c8f75" xlink:to="loc_arwr_InducementAwardsMember_e58d78ed-6a6a-45ab-bdce-47d6ccd18b10" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_49c2ac33-d70d-46be-a795-1cb35715a987" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e6eac579-cd84-4455-908d-6528e9768d4b" xlink:to="loc_us-gaap_AwardTypeAxis_49c2ac33-d70d-46be-a795-1cb35715a987" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_49c2ac33-d70d-46be-a795-1cb35715a987_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_49c2ac33-d70d-46be-a795-1cb35715a987" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_49c2ac33-d70d-46be-a795-1cb35715a987_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e5f96427-f969-4813-b9f3-960fc80ad7d9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_49c2ac33-d70d-46be-a795-1cb35715a987" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e5f96427-f969-4813-b9f3-960fc80ad7d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_b8400876-06c4-4dbc-a22e-a8d80dde1237" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e5f96427-f969-4813-b9f3-960fc80ad7d9" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_b8400876-06c4-4dbc-a22e-a8d80dde1237" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_0d699aeb-f6a4-421e-815b-374e69a0dfe1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_e21fb069-66a2-4b0a-8544-ea218dda85db" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_0d699aeb-f6a4-421e-815b-374e69a0dfe1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_b68f40c0-7f95-48c1-b385-531d3a2bd932" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_e21fb069-66a2-4b0a-8544-ea218dda85db" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_b68f40c0-7f95-48c1-b385-531d3a2bd932" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAndEquityInstrumentsOtherThanOptionsOutstanding_abbb5c93-acd5-4004-8631-769547ace47e" xlink:href="arwr-20231231.xsd#arwr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAndEquityInstrumentsOtherThanOptionsOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_e21fb069-66a2-4b0a-8544-ea218dda85db" xlink:to="loc_arwr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAndEquityInstrumentsOtherThanOptionsOutstanding_abbb5c93-acd5-4004-8631-769547ace47e" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationExpensesIncludedinOperatingExpensesDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#StockBasedCompensationExpensesIncludedinOperatingExpensesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationExpensesIncludedinOperatingExpensesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_ff27f3c6-28b7-4de8-8e88-572f82849dc3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_a8cf8397-79dd-4c68-a705-6a0585ddc909" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_ff27f3c6-28b7-4de8-8e88-572f82849dc3" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_a8cf8397-79dd-4c68-a705-6a0585ddc909" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_f1ff0aad-642a-4437-bac8-fbbe0dd1ea3b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_a8cf8397-79dd-4c68-a705-6a0585ddc909" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_f1ff0aad-642a-4437-bac8-fbbe0dd1ea3b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_f1ff0aad-642a-4437-bac8-fbbe0dd1ea3b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_f1ff0aad-642a-4437-bac8-fbbe0dd1ea3b" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_f1ff0aad-642a-4437-bac8-fbbe0dd1ea3b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_17ba68f3-63a3-4922-a6c0-c13974c67ba4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_f1ff0aad-642a-4437-bac8-fbbe0dd1ea3b" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_17ba68f3-63a3-4922-a6c0-c13974c67ba4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_a72eeff3-4666-4e54-b440-fb20490f4248" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_17ba68f3-63a3-4922-a6c0-c13974c67ba4" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_a72eeff3-4666-4e54-b440-fb20490f4248" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_b46744c5-f374-46a9-9853-2aa7eab174f4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_17ba68f3-63a3-4922-a6c0-c13974c67ba4" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_b46744c5-f374-46a9-9853-2aa7eab174f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_c2455e14-8050-4113-a469-6a120949bb37" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_ff27f3c6-28b7-4de8-8e88-572f82849dc3" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_c2455e14-8050-4113-a469-6a120949bb37" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofRSUsActivityDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#StockBasedCompensationSummaryofRSUsActivityDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofRSUsActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_29d78242-9470-4901-b45d-c508f9f1e482" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d1d30f7f-c087-450f-ba29-9751da6a973c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_29d78242-9470-4901-b45d-c508f9f1e482" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d1d30f7f-c087-450f-ba29-9751da6a973c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_7a7aab9e-5d50-488b-b8c2-d74e66aea9a2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d1d30f7f-c087-450f-ba29-9751da6a973c" xlink:to="loc_us-gaap_AwardTypeAxis_7a7aab9e-5d50-488b-b8c2-d74e66aea9a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7a7aab9e-5d50-488b-b8c2-d74e66aea9a2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_7a7aab9e-5d50-488b-b8c2-d74e66aea9a2" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7a7aab9e-5d50-488b-b8c2-d74e66aea9a2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f5789639-8365-4567-bf7f-97c043ed9e4d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_7a7aab9e-5d50-488b-b8c2-d74e66aea9a2" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f5789639-8365-4567-bf7f-97c043ed9e4d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_740ffeda-9486-4b49-8b59-d54e4c8f4e45" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f5789639-8365-4567-bf7f-97c043ed9e4d" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_740ffeda-9486-4b49-8b59-d54e4c8f4e45" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_35a0ca85-73ff-4b68-a2e7-c4b8b5258c73" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_29d78242-9470-4901-b45d-c508f9f1e482" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_35a0ca85-73ff-4b68-a2e7-c4b8b5258c73" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01373919-7f47-4883-b942-fcf0f325a8ba" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_35a0ca85-73ff-4b68-a2e7-c4b8b5258c73" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01373919-7f47-4883-b942-fcf0f325a8ba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_8f8eeffc-0b9f-4a43-9d7c-c42a4c1adff4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_35a0ca85-73ff-4b68-a2e7-c4b8b5258c73" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_8f8eeffc-0b9f-4a43-9d7c-c42a4c1adff4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_7918d0ae-4eaa-47c1-b4b0-2a272feadbe0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_35a0ca85-73ff-4b68-a2e7-c4b8b5258c73" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_7918d0ae-4eaa-47c1-b4b0-2a272feadbe0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_da412f31-b9a0-494d-9902-0c2c83cfbcd7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_35a0ca85-73ff-4b68-a2e7-c4b8b5258c73" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_da412f31-b9a0-494d-9902-0c2c83cfbcd7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_b66cb9c5-bf5d-42e7-8df3-9b97811222e6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5e7dea74-05c5-4874-a8b1-f50ecfee4439" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_29d78242-9470-4901-b45d-c508f9f1e482" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5e7dea74-05c5-4874-a8b1-f50ecfee4439" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_eeefddcc-9ae6-4dd6-abdd-c259d97d91de" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5e7dea74-05c5-4874-a8b1-f50ecfee4439" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_eeefddcc-9ae6-4dd6-abdd-c259d97d91de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_e8e85c3b-94d5-43fc-ab9f-aaff780ea9a2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5e7dea74-05c5-4874-a8b1-f50ecfee4439" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_e8e85c3b-94d5-43fc-ab9f-aaff780ea9a2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_41b51b51-e6ed-4e6e-8588-479558afbb79" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5e7dea74-05c5-4874-a8b1-f50ecfee4439" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_41b51b51-e6ed-4e6e-8588-479558afbb79" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_afdf3f37-de49-4475-bcda-53a6cb2cd252" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5e7dea74-05c5-4874-a8b1-f50ecfee4439" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_afdf3f37-de49-4475-bcda-53a6cb2cd252" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_60b1f930-a50e-42c1-b637-3c148092df66" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/FairValueMeasurementsFairValueMeasurementsforAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#FairValueMeasurementsFairValueMeasurementsforAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/FairValueMeasurementsFairValueMeasurementsforAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9cbf7fcd-15ef-4247-9391-9e8d73b9fef9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ff88cd8f-b0f6-40e0-9aba-0da0ea030094" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9cbf7fcd-15ef-4247-9391-9e8d73b9fef9" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ff88cd8f-b0f6-40e0-9aba-0da0ea030094" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_d5492ff8-76f2-4d3c-bb29-75ff4fafcccb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ff88cd8f-b0f6-40e0-9aba-0da0ea030094" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_d5492ff8-76f2-4d3c-bb29-75ff4fafcccb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_d5492ff8-76f2-4d3c-bb29-75ff4fafcccb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_d5492ff8-76f2-4d3c-bb29-75ff4fafcccb" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_d5492ff8-76f2-4d3c-bb29-75ff4fafcccb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_680833f6-8b15-4aff-8b36-4bb2921b00fe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_d5492ff8-76f2-4d3c-bb29-75ff4fafcccb" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_680833f6-8b15-4aff-8b36-4bb2921b00fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_c4f7f704-9f67-4483-a759-05b390b8805b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_680833f6-8b15-4aff-8b36-4bb2921b00fe" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_c4f7f704-9f67-4483-a759-05b390b8805b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ffc23d48-0f23-44f4-a0f0-5e3b640ca72c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ff88cd8f-b0f6-40e0-9aba-0da0ea030094" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ffc23d48-0f23-44f4-a0f0-5e3b640ca72c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_ffc23d48-0f23-44f4-a0f0-5e3b640ca72c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ffc23d48-0f23-44f4-a0f0-5e3b640ca72c" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_ffc23d48-0f23-44f4-a0f0-5e3b640ca72c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_0e23e22b-6c5e-40ea-ad03-20fb46c95521" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ffc23d48-0f23-44f4-a0f0-5e3b640ca72c" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_0e23e22b-6c5e-40ea-ad03-20fb46c95521" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_2012f9d5-f1b0-4d9b-977b-371513389437" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_0e23e22b-6c5e-40ea-ad03-20fb46c95521" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_2012f9d5-f1b0-4d9b-977b-371513389437" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_a666a9bb-eeab-4d6f-814a-79579147719f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_0e23e22b-6c5e-40ea-ad03-20fb46c95521" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_a666a9bb-eeab-4d6f-814a-79579147719f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_a2937865-542d-43ff-9561-7526e6bf1a0e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_0e23e22b-6c5e-40ea-ad03-20fb46c95521" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_a2937865-542d-43ff-9561-7526e6bf1a0e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_3aea4129-b44b-45dd-aba5-5eeb8391ee80" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ff88cd8f-b0f6-40e0-9aba-0da0ea030094" xlink:to="loc_us-gaap_FinancialInstrumentAxis_3aea4129-b44b-45dd-aba5-5eeb8391ee80" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_3aea4129-b44b-45dd-aba5-5eeb8391ee80_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_3aea4129-b44b-45dd-aba5-5eeb8391ee80" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_3aea4129-b44b-45dd-aba5-5eeb8391ee80_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_62ea6fe0-04a0-4156-a33d-8545a1771e78" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_3aea4129-b44b-45dd-aba5-5eeb8391ee80" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_62ea6fe0-04a0-4156-a33d-8545a1771e78" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentDebtSecuritiesMember_877de335-ec81-41a0-b669-c01ac33250bd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_USGovernmentDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_62ea6fe0-04a0-4156-a33d-8545a1771e78" xlink:to="loc_us-gaap_USGovernmentDebtSecuritiesMember_877de335-ec81-41a0-b669-c01ac33250bd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MunicipalBondsMember_5aad1700-dc59-46b9-b848-ee4963d669aa" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_MunicipalBondsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_62ea6fe0-04a0-4156-a33d-8545a1771e78" xlink:to="loc_us-gaap_MunicipalBondsMember_5aad1700-dc59-46b9-b848-ee4963d669aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommercialNotesMember_e2e10d14-bdff-419f-b2ac-6ca59fc946d8" xlink:href="arwr-20231231.xsd#arwr_CommercialNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_62ea6fe0-04a0-4156-a33d-8545a1771e78" xlink:to="loc_arwr_CommercialNotesMember_e2e10d14-bdff-419f-b2ac-6ca59fc946d8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_1335f440-2e55-4d53-926e-d37e47e7bec1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_62ea6fe0-04a0-4156-a33d-8545a1771e78" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_1335f440-2e55-4d53-926e-d37e47e7bec1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAxis_8071d220-b08a-41da-a9c6-110d990cd567" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_ff88cd8f-b0f6-40e0-9aba-0da0ea030094" xlink:to="loc_us-gaap_CashAndCashEquivalentsAxis_8071d220-b08a-41da-a9c6-110d990cd567" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_8071d220-b08a-41da-a9c6-110d990cd567_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_8071d220-b08a-41da-a9c6-110d990cd567" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_8071d220-b08a-41da-a9c6-110d990cd567_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_3d22d8db-92c8-4ce4-88c4-552a536de63a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_8071d220-b08a-41da-a9c6-110d990cd567" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_3d22d8db-92c8-4ce4-88c4-552a536de63a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_ca6c1ae3-46e8-4335-b8d6-10acdc84218f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_3d22d8db-92c8-4ce4-88c4-552a536de63a" xlink:to="loc_us-gaap_MoneyMarketFundsMember_ca6c1ae3-46e8-4335-b8d6-10acdc84218f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_fbb4f330-32c2-41ec-865f-6105c2962b99" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9cbf7fcd-15ef-4247-9391-9e8d73b9fef9" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_fbb4f330-32c2-41ec-865f-6105c2962b99" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_71e4574f-5ef1-4146-ac3c-21c6b8a2288f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9cbf7fcd-15ef-4247-9391-9e8d73b9fef9" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_71e4574f-5ef1-4146-ac3c-21c6b8a2288f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_0dc2e1bb-0f88-4967-bd75-3559e6de1272" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9cbf7fcd-15ef-4247-9391-9e8d73b9fef9" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_0dc2e1bb-0f88-4967-bd75-3559e6de1272" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/LiabilityRelatedtotheSaleofFutureRoyaltiesDetails" xlink:type="simple" xlink:href="arwr-20231231.xsd#LiabilityRelatedtotheSaleofFutureRoyaltiesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/LiabilityRelatedtotheSaleofFutureRoyaltiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_cd46472d-f6bc-4035-8ba4-8992dd3888ef" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_cd46472d-f6bc-4035-8ba4-8992dd3888ef" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_32cf55c6-3493-4cec-95b0-cf7a57fe87c9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_cd46472d-f6bc-4035-8ba4-8992dd3888ef" xlink:to="loc_us-gaap_TypeOfArrangementAxis_32cf55c6-3493-4cec-95b0-cf7a57fe87c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_32cf55c6-3493-4cec-95b0-cf7a57fe87c9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_32cf55c6-3493-4cec-95b0-cf7a57fe87c9" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_32cf55c6-3493-4cec-95b0-cf7a57fe87c9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b2f4d514-bf04-42ab-bab2-b32d6690ce23" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_32cf55c6-3493-4cec-95b0-cf7a57fe87c9" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b2f4d514-bf04-42ab-bab2-b32d6690ce23" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_RoyaltyPharmaAgreementMember_628d67e0-26e4-416d-b74a-b1625ff4773d" xlink:href="arwr-20231231.xsd#arwr_RoyaltyPharmaAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b2f4d514-bf04-42ab-bab2-b32d6690ce23" xlink:to="loc_arwr_RoyaltyPharmaAgreementMember_628d67e0-26e4-416d-b74a-b1625ff4773d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_c24e668d-dc6e-42c7-8fc9-ff3299bdde00" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_cd46472d-f6bc-4035-8ba4-8992dd3888ef" xlink:to="loc_srt_RangeAxis_c24e668d-dc6e-42c7-8fc9-ff3299bdde00" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_c24e668d-dc6e-42c7-8fc9-ff3299bdde00_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_c24e668d-dc6e-42c7-8fc9-ff3299bdde00" xlink:to="loc_srt_RangeMember_c24e668d-dc6e-42c7-8fc9-ff3299bdde00_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_844f2c3d-2e40-42af-b281-88f17f2f22b7" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_c24e668d-dc6e-42c7-8fc9-ff3299bdde00" xlink:to="loc_srt_RangeMember_844f2c3d-2e40-42af-b281-88f17f2f22b7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_dd8da93b-36d5-4313-a13e-58e2fa8e8b0f" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_844f2c3d-2e40-42af-b281-88f17f2f22b7" xlink:to="loc_srt_MaximumMember_dd8da93b-36d5-4313-a13e-58e2fa8e8b0f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_9d44edf8-027b-4896-b924-924462fce570" xlink:href="arwr-20231231.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_InitialTransactionPrice_9d44edf8-027b-4896-b924-924462fce570" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CashReceivedAsDueUnderCollaborationAgreement_9f6996b0-342e-46b6-88a1-fd4a8c72dbaf" xlink:href="arwr-20231231.xsd#arwr_CashReceivedAsDueUnderCollaborationAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_CashReceivedAsDueUnderCollaborationAgreement_9f6996b0-342e-46b6-88a1-fd4a8c72dbaf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivable_087ceb79-dfa2-46b8-a671-a57b59eb4279" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_MilestonePaymentReceivable_087ceb79-dfa2-46b8-a671-a57b59eb4279" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponAchievementOfEnrollmentInPhase3ClinicalTrial_c109e695-3f8a-49e3-a789-5fca4d15a9df" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentReceivableUponAchievementOfEnrollmentInPhase3ClinicalTrial"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_MilestonePaymentReceivableUponAchievementOfEnrollmentInPhase3ClinicalTrial_c109e695-3f8a-49e3-a789-5fca4d15a9df" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponFDAApproval_fb35bfd0-6fdb-4ef2-bc6a-b5ee693e59bc" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentReceivableUponFDAApproval"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_MilestonePaymentReceivableUponFDAApproval_fb35bfd0-6fdb-4ef2-bc6a-b5ee693e59bc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponReceiptOfRoyaltyPayments_0833a7d3-4675-421f-b110-b67005c4e5ac" xlink:href="arwr-20231231.xsd#arwr_MilestonePaymentReceivableUponReceiptOfRoyaltyPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_MilestonePaymentReceivableUponReceiptOfRoyaltyPayments_0833a7d3-4675-421f-b110-b67005c4e5ac" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_RoyaltyPaymentThreshold_54db82d1-602f-4c50-8db9-005d35b93434" xlink:href="arwr-20231231.xsd#arwr_RoyaltyPaymentThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_RoyaltyPaymentThreshold_54db82d1-602f-4c50-8db9-005d35b93434" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_LiabilitySaleOfFutureRoyalties_bc1c357f-566e-471f-a5aa-6657be9addd8" xlink:href="arwr-20231231.xsd#arwr_LiabilitySaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_LiabilitySaleOfFutureRoyalties_bc1c357f-566e-471f-a5aa-6657be9addd8" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NonCashInterestExpenseLiabilityRelatedToSaleOfFutureRoyalties_b719c9e8-f029-42b5-871e-7a58c063cc4b" xlink:href="arwr-20231231.xsd#arwr_NonCashInterestExpenseLiabilityRelatedToSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_49067c21-7a81-4f93-a69f-138848ea7093" xlink:to="loc_arwr_NonCashInterestExpenseLiabilityRelatedToSaleOfFutureRoyalties_b719c9e8-f029-42b5-871e-7a58c063cc4b" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/AwardTypeOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2023/ecd-2023.xsd#AwardTypeOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/AwardTypeOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember" xlink:type="arc" order="4"/>
  </link:definitionLink>
</link:linkbase>
