diff --git a/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base.cc b/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base.cc
index 2340f1446aec4..633010d5e0d58 100644
--- a/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base.cc
+++ b/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base.cc
@@ -357,7 +357,13 @@ void MultipleRequestPaymentsNetworkInterfaceBase::RequestOperation::
 void MultipleRequestPaymentsNetworkInterfaceBase::RequestOperation::
     ReportOperationResult(PaymentsRpcResult result) {
   CHECK(request_);
+  // RespondToDelegate may delete `payments_network_interface_` (and with it
+  // `this`) if its owner is torn down from within the response callback.
+  auto weak_this = weak_ptr_factory_.GetWeakPtr();
   request_->RespondToDelegate(result);
+  if (!weak_this) {
+    return;
+  }
   payments_network_interface_->OnRequestFinished(request_operation_id_);
 }
 
diff --git a/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base_unittest.cc b/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base_unittest.cc
index 3e01d9ed2814d..4e2f46e6badde 100644
--- a/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base_unittest.cc
+++ b/components/autofill/core/browser/payments/multiple_request_payments_network_interface_base_unittest.cc
@@ -265,4 +265,20 @@ TEST_F(MultipleRequestsTest, RequestCanceled) {
   EXPECT_EQ(0U, operations_size());
 }
 
+// A request's RespondToDelegate may synchronously destroy the network
+// interface (and thus the in-flight RequestOperation) if its owner outlives
+// neither.
+TEST_F(MultipleRequestsTest, RespondToDelegateDestroysNetworkInterface) {
+  EXPECT_CALL(*request1_, RespondToDelegate(PaymentsRpcResult::kSuccess))
+      .WillOnce([&](PaymentsRpcResult) {
+        payments_network_interface_base_.reset();
+      });
+
+  RequestId id1 =
+      payments_network_interface_base_->IssueRequest(std::move(request1_));
+  IssueOAuthToken();
+  ReturnResponseForOperation(id1, net::HTTP_OK, "{}");
+  EXPECT_FALSE(payments_network_interface_base_);
+}
+
 }  // namespace autofill::payments
diff --git a/components/autofill/core/browser/payments/virtual_card_enrollment_manager.cc b/components/autofill/core/browser/payments/virtual_card_enrollment_manager.cc
index 55a6bf0ca87af..2a7eb27147e42 100644
--- a/components/autofill/core/browser/payments/virtual_card_enrollment_manager.cc
+++ b/components/autofill/core/browser/payments/virtual_card_enrollment_manager.cc
@@ -347,17 +347,20 @@ void VirtualCardEnrollmentManager::OnDidGetUpdateVirtualCardEnrollmentResponse(
         state_.virtual_card_enrollment_fields.credit_card.instrument_id()));
   }
 
-  // Relay the response to the server card editor page. This also destroys the
-  // payments delegate if the editor was already closed.
-  if (virtual_card_enrollment_update_response_callback_.has_value()) {
-    std::move(virtual_card_enrollment_update_response_callback_.value())
-        .Run(result);
-  }
-
   LogUpdateVirtualCardEnrollmentRequestResult(
       state_.virtual_card_enrollment_fields.virtual_card_enrollment_source,
       type, result == PaymentsRpcResult::kSuccess);
+
+  std::optional<VirtualCardEnrollmentUpdateResponseCallback> response_callback =
+      std::move(virtual_card_enrollment_update_response_callback_);
   Reset();
+
+  // Relay the response to the server card editor page. This may destroy the
+  // payments delegate (and with it `this`) if the editor was already closed,
+  // so it must run last.
+  if (response_callback.has_value()) {
+    std::move(response_callback.value()).Run(result);
+  }
 }
 
 void VirtualCardEnrollmentManager::OnVirtualCardEnrollCompleted(
diff --git a/components/autofill/core/browser/payments/virtual_card_enrollment_manager_unittest.cc b/components/autofill/core/browser/payments/virtual_card_enrollment_manager_unittest.cc
index af5c7e242a309..9b4bea2e174b8 100644
--- a/components/autofill/core/browser/payments/virtual_card_enrollment_manager_unittest.cc
+++ b/components/autofill/core/browser/payments/virtual_card_enrollment_manager_unittest.cc
@@ -8,6 +8,7 @@
 #include "base/functional/callback.h"
 #include "base/strings/strcat.h"
 #include "base/strings/string_number_conversions.h"
+#include "base/test/bind.h"
 #include "base/test/metrics/histogram_tester.h"
 #include "base/test/mock_callback.h"
 #include "base/test/scoped_feature_list.h"
@@ -404,6 +405,50 @@ TEST_F(VirtualCardEnrollmentManagerTest, Unenroll) {
       /*sample=*/false, 1);
 }
 
+// On the Clank settings page the update-response callback can synchronously
+// destroy the owning delegate (and with it, this manager) when the editor was
+// closed while a request was in flight. The manager must finish all of its own
+// work before invoking that callback.
+TEST_F(VirtualCardEnrollmentManagerTest,
+       Unenroll_ResponseCallbackDeletesManager) {
+  base::HistogramTester histogram_tester;
+  payments_data_manager().SetPaymentsCustomerData(
+      std::make_unique<PaymentsCustomerData>(/*customer_id=*/"123456"));
+
+  base::OnceCallback<void(payments::PaymentsAutofillClient::PaymentsRpcResult)>
+      network_response_callback;
+  EXPECT_CALL(multiple_request_payments_network_interface(),
+              UpdateVirtualCardEnrollment)
+      .WillOnce(
+          [&](const payments::UpdateVirtualCardEnrollmentRequestDetails&,
+              base::OnceCallback<void(
+                  payments::PaymentsAutofillClient::PaymentsRpcResult)>
+                  callback) {
+            network_response_callback = std::move(callback);
+            return payments::RequestId("11223344");
+          });
+
+  bool response_received = false;
+  virtual_card_enrollment_manager_->Unenroll(
+      /*instrument_id=*/9223372036854775807,
+      /*virtual_card_enrollment_update_response_callback=*/
+      base::BindLambdaForTesting(
+          [&](payments::PaymentsAutofillClient::PaymentsRpcResult) {
+            response_received = true;
+            virtual_card_enrollment_manager_.reset();
+          }));
+
+  ASSERT_FALSE(network_response_callback.is_null());
+  std::move(network_response_callback)
+      .Run(payments::PaymentsAutofillClient::PaymentsRpcResult::kSuccess);
+
+  EXPECT_TRUE(response_received);
+  EXPECT_FALSE(virtual_card_enrollment_manager_);
+  histogram_tester.ExpectBucketCount(
+      "Autofill.VirtualCard.Unenroll.Result.SettingsPage",
+      /*sample=*/true, 1);
+}
+
 #if !BUILDFLAG(IS_IOS)
 TEST_F(VirtualCardEnrollmentManagerTest, StrikeDatabase_BubbleAccepted) {
   base::HistogramTester histogram_tester;