diff --git a/packages/react-reconciler/src/ReactFiberThenable.js b/packages/react-reconciler/src/ReactFiberThenable.js
index 643be63ffa1c..b8b6c5d4b852 100644
--- a/packages/react-reconciler/src/ReactFiberThenable.js
+++ b/packages/react-reconciler/src/ReactFiberThenable.js
@@ -192,12 +192,30 @@ export function trackUsedThenable<T>(
   // a listener that will update its status and result when it resolves.
   switch (thenable.status) {
     case 'fulfilled': {
+      // This could be a bad instrumentation that doesn't set .value.
+      // We're not type-checking since this is a hot path where you can
+      // track down easily when something becomes `undefined` unexpectedly.
       const fulfilledValue: T = thenable.value;
       return fulfilledValue;
     }
     case 'rejected': {
       const rejectedError = thenable.reason;
       checkIfUseWrappedInAsyncCatch(rejectedError);
+
+      // Rejected Promises are rarer so we're doing an extra type-check in
+      // case of a bad instrumentation that doesn't set .reason
+      // If we end up throwing `undefined` it becomes hard to track down
+      // where that throw originated because no callstack would exist.
+      // React would still have a Component stack but that could only be used
+      // as an approximation.
+      if (rejectedError === undefined && !('reason' in thenable)) {
+        throw new Error(
+          'A rejected Promise was passed to React without a `reason` property. ' +
+            'React threw a generic error from where the Promise was used to assist in identifying the problematic Promise. ' +
+            "Make sure that instrumented Promises correctly set the `reason` property when setting `status` to `'rejected'`.",
+        );
+      }
+
       throw rejectedError;
     }
     default: {
diff --git a/packages/react-reconciler/src/__tests__/ReactUse-test.js b/packages/react-reconciler/src/__tests__/ReactUse-test.js
index 9714cb4a3e2e..7b4bd5c1c61c 100644
--- a/packages/react-reconciler/src/__tests__/ReactUse-test.js
+++ b/packages/react-reconciler/src/__tests__/ReactUse-test.js
@@ -81,6 +81,30 @@ describe('ReactUse', () => {
     });
   }
 
+  function normalizeCodeLocInfo(str) {
+    return (
+      str &&
+      str.replace(
+        /^ +(?:at|in) ([\S]+)([^\n]*)(\n?)/gm,
+        function (m, name, location, eol) {
+          if (location.indexOf(__filename) === -1) {
+            // ignore frames from library code
+            return '';
+          }
+          return (
+            '    in ' +
+            name +
+            (/:\d+:\d+/.test(m)
+              ? ' ' +
+                location.replace(__dirname, '~').replace(/:\d+:\d+/, ':*:*')
+              : '') +
+            eol
+          );
+        },
+      )
+    );
+  }
+
   function Text({text}) {
     Scheduler.log(text);
     return text;
@@ -2189,4 +2213,108 @@ describe('ReactUse', () => {
       expect(root).toMatchRenderedOutput('Updated');
     },
   );
+
+  it('throws a descriptive error when a rejected promise without a reason property is passed to use()', async () => {
+    const badThenable = Promise.resolve();
+    // Simulate bad instrumentation: status is 'rejected' but the reason is not
+    // in the `reason` property as intended.
+    badThenable.status = 'rejected';
+    badThenable.error = new Error('Something went wrong');
+
+    function Child() {
+      return use(badThenable);
+    }
+
+    function App({
+      // Intentionally destrucutring a prop here so that our production error
+      // stack trick is triggered at the beginning of the function
+      prop,
+    }) {
+      return <Child />;
+    }
+
+    const uncaughtErrors = [];
+    const root = ReactNoop.createRoot({
+      onUncaughtError(error, errorInfo) {
+        uncaughtErrors.push({
+          callStack: normalizeCodeLocInfo(error.stack),
+          ownerStack: React.captureOwnerStack
+            ? normalizeCodeLocInfo(React.captureOwnerStack())
+            : null,
+          componentStack: normalizeCodeLocInfo(errorInfo.componentStack),
+        });
+      },
+    });
+
+    await act(() => {
+      root.render(<App />);
+    });
+
+    expect(uncaughtErrors).toEqual([
+      {
+        callStack:
+          'Error: A rejected Promise was passed to React without a `reason` property. ' +
+          'React threw a generic error from where the Promise was used to assist in identifying the problematic Promise. ' +
+          "Make sure that instrumented Promises correctly set the `reason` property when setting `status` to `'rejected'`." +
+          '\n    in Child  (~/ReactUse-test.js:*:*)' +
+          '\n    in Object.<anonymous>  (~/ReactUse-test.js:*:*)',
+        componentStack:
+          '\n    in Child  (~/ReactUse-test.js:*:*)' +
+          '\n    in App  (~/ReactUse-test.js:*:*)',
+        ownerStack: __DEV__ ? '\n    in App  (~/ReactUse-test.js:*:*)' : null,
+      },
+    ]);
+  });
+
+  it('throws a descriptive error when a rejected promise without a reason property is used as a child', async () => {
+    const badThenable = Promise.resolve();
+    // Simulate bad instrumentation: status is 'rejected' but the reason is not
+    // in the `reason` property as intended.
+    badThenable.status = 'rejected';
+    badThenable.error = new Error('Something went wrong');
+
+    function Child() {
+      return <div>{badThenable}</div>;
+    }
+
+    function App({
+      // Intentionally destrucutring a prop here so that our production error
+      // stack trick is triggered at the beginning of the function
+      prop,
+    }) {
+      return <Child />;
+    }
+
+    const uncaughtErrors = [];
+    const root = ReactNoop.createRoot({
+      onUncaughtError(error, errorInfo) {
+        uncaughtErrors.push({
+          callStack: normalizeCodeLocInfo(error.stack),
+          ownerStack: React.captureOwnerStack
+            ? normalizeCodeLocInfo(React.captureOwnerStack())
+            : null,
+          componentStack: normalizeCodeLocInfo(errorInfo.componentStack),
+        });
+      },
+    });
+
+    await act(() => {
+      root.render(<App />);
+    });
+
+    expect(uncaughtErrors).toEqual([
+      {
+        callStack:
+          'Error: A rejected Promise was passed to React without a `reason` property. ' +
+          'React threw a generic error from where the Promise was used to assist in identifying the problematic Promise. ' +
+          "Make sure that instrumented Promises correctly set the `reason` property when setting `status` to `'rejected'`." +
+          '\n    in Object.<anonymous>  (~/ReactUse-test.js:*:*)',
+        componentStack: '\n    in App  (~/ReactUse-test.js:*:*)',
+        ownerStack: __DEV__
+          ? // TODO: Should start in Child since that's the owner.
+            '\n    in App  (~/ReactUse-test.js:*:*)'
+          : null,
+      },
+    ]);
+  });
 });
diff --git a/packages/react-server/src/ReactFizzThenable.js b/packages/react-server/src/ReactFizzThenable.js
index 6849f16e397d..65eeddc4962f 100644
--- a/packages/react-server/src/ReactFizzThenable.js
+++ b/packages/react-server/src/ReactFizzThenable.js
@@ -69,11 +69,29 @@ export function trackUsedThenable<T>(
   // a listener that will update its status and result when it resolves.
   switch (thenable.status) {
     case 'fulfilled': {
+      // This could be a bad instrumentation that doesn't set .value.
+      // We're not type-checking since this is a hot path where you can
+      // track down easily when something becomes `undefined` unexpectedly.
       const fulfilledValue: T = thenable.value;
       return fulfilledValue;
     }
     case 'rejected': {
       const rejectedError = thenable.reason;
+
+      // Rejected Promises are rarer so we're doing an extra type-check in
+      // case of a bad instrumentation that doesn't set .reason
+      // If we end up throwing `undefined` it becomes hard to track down
+      // where that throw originated because no callstack would exist.
+      // React would still have a Component stack but that could only be used
+      // as an approximation.
+      if (rejectedError === undefined && !('reason' in thenable)) {
+        throw new Error(
+          'A rejected Promise was passed to React without a `reason` property. ' +
+            'React threw a generic error from where the Promise was used to assist in identifying the problematic Promise. ' +
+            "Make sure that instrumented Promises correctly set the `reason` property when setting `status` to `'rejected'`.",
+        );
+      }
+
       throw rejectedError;
     }
     default: {
diff --git a/packages/react-server/src/ReactFlightThenable.js b/packages/react-server/src/ReactFlightThenable.js
index 99ddb36fa599..9c0c8082facb 100644
--- a/packages/react-server/src/ReactFlightThenable.js
+++ b/packages/react-server/src/ReactFlightThenable.js
@@ -77,11 +77,29 @@ export function trackUsedThenable<T>(
   // a listener that will update its status and result when it resolves.
   switch (thenable.status) {
     case 'fulfilled': {
+      // This could be a bad instrumentation that doesn't set .value.
+      // We're not type-checking since this is a hot path where you can
+      // track down easily when something becomes `undefined` unexpectedly.
       const fulfilledValue: T = thenable.value;
       return fulfilledValue;
     }
     case 'rejected': {
       const rejectedError = thenable.reason;
+
+      // Rejected Promises are rarer so we're doing an extra type-check in
+      // case of a bad instrumentation that doesn't set .reason
+      // If we end up throwing `undefined` it becomes hard to track down
+      // where that throw originated because no callstack would exist.
+      // React would still have a Component stack but that could only be used
+      // as an approximation.
+      if (rejectedError === undefined && !('reason' in thenable)) {
+        throw new Error(
+          'A rejected Promise was passed to React without a `reason` property. ' +
+            'React threw a generic error from where the Promise was used to assist in identifying the problematic Promise. ' +
+            "Make sure that instrumented Promises correctly set the `reason` property when setting `status` to `'rejected'`.",
+        );
+      }
+
       throw rejectedError;
     }
     default: {
diff --git a/scripts/error-codes/codes.json b/scripts/error-codes/codes.json
index 345aa2b0aaf0..87fd927000c6 100644
--- a/scripts/error-codes/codes.json
+++ b/scripts/error-codes/codes.json
@@ -582,5 +582,6 @@
   "594": "Cannot read Symbol exports. Only named exports are supported on a client module imported on the server.",
   "595": "Attempted to call %s() from the server but %s is on the client. It's not possible to invoke a client function from the server, it can only be rendered as a Component or passed to props of a Client Component.",
   "596": "Could not find the module \"%s\" in the React Client Manifest. This is probably a bug in the React Server Components bundler.",
-  "597": "The module \"%s\" is marked as an async ESM module but was loaded as a CJS proxy. This is probably a bug in the React Server Components bundler."
-}
\ No newline at end of file
+  "597": "The module \"%s\" is marked as an async ESM module but was loaded as a CJS proxy. This is probably a bug in the React Server Components bundler.",
+  "598": "A rejected Promise was passed to React without a `reason` property. React threw a generic error from where the Promise was used to assist in identifying the problematic Promise. Make sure that instrumented Promises correctly set the `reason` property when setting `status` to `'rejected'`."
+}