diff --git a/packages/react/src/components/createInlineOverlayComponent.tsx b/packages/react/src/components/createInlineOverlayComponent.tsx
index 3d4dab1fef..783ba5b495 100644
--- a/packages/react/src/components/createInlineOverlayComponent.tsx
+++ b/packages/react/src/components/createInlineOverlayComponent.tsx
@@ -78,10 +78,19 @@ export const createInlineOverlayComponent = <PropType, ElementType>(
        * cleanup properly.
        */
       this.ref.current?.addEventListener('didDismiss', (evt: any) => {
-        const wrapper = this.wrapperRef.current!;
-        this.ref.current!.append(wrapper);
+        const wrapper = this.wrapperRef.current;
+        const el = this.ref.current;
 
-        this.setState({ isOpen: false });
+        /**
+         * This component might be unmounted already, if the containing
+         * element was removed while the popover was still open. (For
+         * example, if an item contains an inline popover with a button
+         * that removes the item.)
+         */
+        if (wrapper && el) {
+          el.append(wrapper);
+          this.setState({ isOpen: false });
+        }
 
         this.props.onDidDismiss && this.props.onDidDismiss(evt);
       });
diff --git a/packages/react/test-app/cypress/integration/overlay-components/IonPopover.spec.ts b/packages/react/test-app/cypress/integration/overlay-components/IonPopover.spec.ts
index df39183deb..9a7eb880a6 100644
--- a/packages/react/test-app/cypress/integration/overlay-components/IonPopover.spec.ts
+++ b/packages/react/test-app/cypress/integration/overlay-components/IonPopover.spec.ts
@@ -18,4 +18,12 @@ describe('IonPopover', () => {
     cy.get('ion-popover ion-list-header').contains('Ionic');
   });
 
+  it('display popover and remove containing element', () => {
+    //show popover, remove containing item
+    cy.get('#openPopover').click();
+    cy.get('#removeItem').click();
+
+    //verify popover is gone
+    cy.get('#popoverInItem').should('not.exist');
+  });
 });
diff --git a/packages/react/test-app/src/pages/overlay-components/PopoverComponent.tsx b/packages/react/test-app/src/pages/overlay-components/PopoverComponent.tsx
index 6c0bfe9aa3..0d02dc53cd 100644
--- a/packages/react/test-app/src/pages/overlay-components/PopoverComponent.tsx
+++ b/packages/react/test-app/src/pages/overlay-components/PopoverComponent.tsx
@@ -30,6 +30,8 @@ const PopoverComponent: React.FC = () => {
     event: undefined,
   });
 
+  const [renderItem, setRenderItem] = useState(true);
+
   return (
     <IonPage>
       <IonContent>
@@ -70,6 +72,12 @@ const PopoverComponent: React.FC = () => {
         >
           Show Popover, hide after 250 ms
         </IonButton>
+        {renderItem && <IonItem>
+          <IonButton id="openPopover">Open</IonButton>
+          <IonPopover id="popoverInItem" trigger="openPopover" dismissOnSelect={true}>
+            <IonButton id="removeItem" onClick={() => setRenderItem(false)}>Remove Item</IonButton>
+          </IonPopover>
+        </IonItem>}
       </IonContent>
     </IonPage>
   );