diff --git a/extensions/browser/app_window/app_window.cc b/extensions/browser/app_window/app_window.cc
index b704f7e6b76d5..6bef4b5c0b58e 100644
--- a/extensions/browser/app_window/app_window.cc
+++ b/extensions/browser/app_window/app_window.cc
@@ -853,7 +853,15 @@ void AppWindow::DidDownloadFavicon(
 }
 
 void AppWindow::SetNativeWindowFullscreen() {
+  // The platform fullscreen transition (Widget::SetFullscreen ->
+  // ::SetWindowPos / [NSWindow toggleFullScreen:]) may spin a nested message
+  // loop and destroy `this` via OnNativeClose(). See crbug.com/1506535,
+  // crbug.com/498752242.
+  auto weak_this = weak_ptr_factory_.GetWeakPtr();
   native_app_window_->SetFullscreen(fullscreen_types_);
+  if (!weak_this) {
+    return;
+  }
 
   RestoreAlwaysOnTop();
 }
diff --git a/extensions/browser/app_window/app_window.h b/extensions/browser/app_window/app_window.h
index 04cca6ea0c2a3..d81320c18425e 100644
--- a/extensions/browser/app_window/app_window.h
+++ b/extensions/browser/app_window/app_window.h
@@ -601,6 +601,8 @@ class AppWindow : public content::WebContentsDelegate,
   base::OnceClosure on_update_draggable_regions_callback_for_testing_;
 
   base::WeakPtrFactory<AppWindow> image_loader_ptr_factory_{this};
+
+  base::WeakPtrFactory<AppWindow> weak_ptr_factory_{this};
 };
 
 }  // namespace extensions