diff --git a/.changes/macos-ipc-handlers-undefined.md b/.changes/macos-ipc-handlers-undefined.md
new file mode 100644
index 000000000..dbc8c33d7
--- /dev/null
+++ b/.changes/macos-ipc-handlers-undefined.md
@@ -0,0 +1,9 @@
+---
+"wry": patch
+---
+
+On macOS, a Tauri v2 app can lose the WebKit message handler used by Tauri IPC after a popup opened via window.open is handled with tauri::webview::NewWindowResponse::Create and then closed.
+
+After this happens, the opener/main window still has Tauri's JavaScript initialization objects, but later invoke() calls fail because window.webkit.messageHandlers becomes undefined which means it is no longer available.
+
+Fixed by removing the IPC message handler only if it is registered/owned by the popup.
diff --git a/src/wkwebview/class/wry_web_view_delegate.rs b/src/wkwebview/class/wry_web_view_delegate.rs
index 58e7d54d3..b98c7427b 100644
--- a/src/wkwebview/class/wry_web_view_delegate.rs
+++ b/src/wkwebview/class/wry_web_view_delegate.rs
@@ -2,7 +2,7 @@
 // SPDX-License-Identifier: Apache-2.0
 // SPDX-License-Identifier: MIT
 
-use std::{ffi::CStr, panic::AssertUnwindSafe};
+use std::{cell::Cell, ffi::CStr, panic::AssertUnwindSafe};
 
 use http::Request;
 use objc2::{
@@ -19,6 +19,7 @@ pub const IPC_MESSAGE_HANDLER_NAME: &str = "ipc";
 pub struct WryWebViewDelegateIvars {
   pub controller: Retained<WKUserContentController>,
   pub ipc_handler: Box<dyn Fn(Request<String>)>,
+  pub registered_ipc_handler: Cell<bool>,
 }
 
 define_class!(
@@ -85,20 +86,26 @@ impl WryWebViewDelegate {
       .set_ivars(WryWebViewDelegateIvars {
         ipc_handler,
         controller,
+        registered_ipc_handler: Cell::new(false),
       });
 
     let delegate: Retained<Self> = unsafe { msg_send![super(delegate), init] };
 
     let proto_delegate = ProtocolObject::from_ref(&*delegate);
-    unsafe {
+    let did_register_ipc_handler = unsafe {
       // this will increase the retain count of the delegate
-      let _res = objc2::exception::catch(AssertUnwindSafe(|| {
+      objc2::exception::catch(AssertUnwindSafe(|| {
         delegate
           .ivars()
           .controller
           .addScriptMessageHandler_name(proto_delegate, ns_string!(IPC_MESSAGE_HANDLER_NAME));
-      }));
-    }
+      }))
+      .is_ok()
+    };
+    delegate
+      .ivars()
+      .registered_ipc_handler
+      .set(did_register_ipc_handler);
 
     delegate
   }
diff --git a/src/wkwebview/mod.rs b/src/wkwebview/mod.rs
index 685634980..072c221be 100644
--- a/src/wkwebview/mod.rs
+++ b/src/wkwebview/mod.rs
@@ -1400,12 +1400,14 @@ impl Drop for InnerWebView {
     // We need to drop handler closures here
     unsafe {
       if let Some(ipc_handler) = self.ipc_handler_delegate.take() {
-        let ipc = ns_string!(IPC_MESSAGE_HANDLER_NAME);
-        // this will decrease the retain count of the ipc handler and trigger the drop
-        ipc_handler
-          .ivars()
-          .controller
-          .removeScriptMessageHandlerForName(ipc);
+        if ipc_handler.ivars().registered_ipc_handler.get() {
+          let ipc = ns_string!(IPC_MESSAGE_HANDLER_NAME);
+          // this will decrease the retain count of the ipc handler and trigger the drop
+          ipc_handler
+            .ivars()
+            .controller
+            .removeScriptMessageHandlerForName(ipc);
+        }
       }
 
       // Remove webview from window's NSView before dropping.