diff --git a/packages/mui-material/src/Tooltip/Tooltip.js b/packages/mui-material/src/Tooltip/Tooltip.js
index 475e05372e3bf2..890945aa5215bd 100644
--- a/packages/mui-material/src/Tooltip/Tooltip.js
+++ b/packages/mui-material/src/Tooltip/Tooltip.js
@@ -476,9 +476,22 @@ const Tooltip = React.forwardRef(function Tooltip(inProps, ref) {
 
   const [, setChildIsFocusVisible] = React.useState(false);
   const handleBlur = (event) => {
-    if (!isFocusVisible(event.target)) {
+    // Needed for https://github.com/mui/material-ui/issues/45373
+    const target = event?.target ?? childNode;
+    if (!target || !isFocusVisible(target)) {
       setChildIsFocusVisible(false);
-      handleMouseLeave(event);
+
+      // InputBase can call onBlur() without an event when the input becomes disabled.
+      // Tooltip must not assume an event object exists.
+      const closeEvent = event ?? new Event('blur');
+
+      // `new Event('blur')` has `target/currentTarget === null`, but Tooltip's close logic
+      // (and user callbacks like onClose) may expect them to reference the anchor element.
+      if (!event && target) {
+        Object.defineProperty(closeEvent, 'target', { value: target });
+        Object.defineProperty(closeEvent, 'currentTarget', { value: target });
+      }
+      handleMouseLeave(closeEvent);
     }
   };
 
diff --git a/packages/mui-material/test/integration/Tooltip.test.js b/packages/mui-material/test/integration/Tooltip.test.js
new file mode 100644
index 00000000000000..d443b66327a6ae
--- /dev/null
+++ b/packages/mui-material/test/integration/Tooltip.test.js
@@ -0,0 +1,50 @@
+import { expect } from 'chai';
+import { createRenderer, screen, isJsdom, act, fireEvent } from '@mui/internal-test-utils';
+import Tooltip from '@mui/material/Tooltip';
+import Input from '@mui/material/Input';
+
+function focusVisibleSync(element) {
+  act(() => {
+    element.blur();
+  });
+  fireEvent.keyDown(document.body, { key: 'Tab' });
+  act(() => {
+    element.focus();
+  });
+}
+
+describe('<Tooltip> integration', () => {
+  const { render } = createRenderer();
+
+  it.skipIf(isJsdom())(
+    'does not throw error and closes Tooltip when Input becomes disabled while focused',
+    () => {
+      function TestCase({ disabled }) {
+        return (
+          <Tooltip
+            title="Test"
+            enterDelay={0}
+            leaveDelay={0}
+            slotProps={{ transition: { timeout: 0 } }}
+          >
+            <Input disabled={disabled} placeholder="click here and wait" />
+          </Tooltip>
+        );
+      }
+
+      const { setProps } = render(<TestCase disabled={false} />);
+
+      const input = screen.getByRole('textbox');
+
+      focusVisibleSync(input);
+
+      expect(screen.getByRole('tooltip')).toBeVisible();
+
+      expect(() => {
+        setProps({ disabled: true });
+      }).not.to.throw();
+
+      expect(screen.getByRole('tooltip')).not.toBeVisible();
+    },
+  );
+});