diff --git a/fixtures/dom/src/components/fixtures/mouse-events/index.js b/fixtures/dom/src/components/fixtures/mouse-events/index.js
index 4c121bf094790..3624d4e837b2f 100644
--- a/fixtures/dom/src/components/fixtures/mouse-events/index.js
+++ b/fixtures/dom/src/components/fixtures/mouse-events/index.js
@@ -1,5 +1,6 @@
 import FixtureSet from '../../FixtureSet';
 import MouseMovement from './mouse-movement';
+import MouseEnter from './mouse-enter';
 
 const React = window.React;
 
@@ -8,6 +9,7 @@ class MouseEvents extends React.Component {
     return (
       <FixtureSet title="Mouse Events">
         <MouseMovement />
+        <MouseEnter />
       </FixtureSet>
     );
   }
diff --git a/fixtures/dom/src/components/fixtures/mouse-events/mouse-enter.js b/fixtures/dom/src/components/fixtures/mouse-events/mouse-enter.js
new file mode 100644
index 0000000000000..c0fbcbda6a432
--- /dev/null
+++ b/fixtures/dom/src/components/fixtures/mouse-events/mouse-enter.js
@@ -0,0 +1,73 @@
+import TestCase from '../../TestCase';
+
+const React = window.React;
+const ReactDOM = window.ReactDOM;
+
+const MouseEnter = () => {
+  const containerRef = React.useRef();
+
+  React.useEffect(function() {
+    const hostEl = containerRef.current;
+    ReactDOM.render(<MouseEnterDetect />, hostEl, () => {
+      ReactDOM.render(<MouseEnterDetect />, hostEl.childNodes[1]);
+    });
+  }, []);
+
+  return (
+    <TestCase
+      title="Mouse Enter"
+      description=""
+      affectedBrowsers="Chrome, Safari, Firefox">
+      <TestCase.Steps>
+        <li>Mouse enter the boxes below, from different borders</li>
+      </TestCase.Steps>
+      <TestCase.ExpectedResult>
+        Mouse enter call count should equal to 1; <br />
+        Issue{' '}
+        <a
+          rel="noopener noreferrer"
+          target="_blank"
+          href="https://github.com/facebook/react/issues/16763">
+          #16763
+        </a>{' '}
+        should not happen.
+        <br />
+      </TestCase.ExpectedResult>
+      <div ref={containerRef} />
+    </TestCase>
+  );
+};
+
+const MouseEnterDetect = () => {
+  const [log, setLog] = React.useState({});
+  const firstEl = React.useRef();
+  const siblingEl = React.useRef();
+
+  const onMouseEnter = e => {
+    const timeStamp = e.timeStamp;
+    setLog(log => {
+      const callCount = 1 + (log.timeStamp === timeStamp ? log.callCount : 0);
+      return {
+        timeStamp,
+        callCount,
+      };
+    });
+  };
+
+  return (
+    <React.Fragment>
+      <div
+        ref={firstEl}
+        onMouseEnter={onMouseEnter}
+        style={{
+          border: '1px solid #d9d9d9',
+          padding: '20px 20px',
+        }}>
+        Mouse enter call count: {log.callCount || ''}
+      </div>
+      <div ref={siblingEl} />
+    </React.Fragment>
+  );
+};
+
+export default MouseEnter;
diff --git a/packages/react-dom/src/events/EnterLeaveEventPlugin.js b/packages/react-dom/src/events/EnterLeaveEventPlugin.js
index 4133006488171..aca141225282e 100644
--- a/packages/react-dom/src/events/EnterLeaveEventPlugin.js
+++ b/packages/react-dom/src/events/EnterLeaveEventPlugin.js
@@ -146,6 +146,10 @@ const EnterLeaveEventPlugin = {
 
     accumulateEnterLeaveDispatches(leave, enter, from, to);
 
+    if (isOutEvent && from && nativeEventTarget !== fromNode) {
+      return [leave];
+    }
+
     return [leave, enter];
   },
 };
diff --git a/packages/react-dom/src/events/__tests__/EnterLeaveEventPlugin-test.js b/packages/react-dom/src/events/__tests__/EnterLeaveEventPlugin-test.js
index 33dd3e964ee40..b8bda1c67fe9f 100644
--- a/packages/react-dom/src/events/__tests__/EnterLeaveEventPlugin-test.js
+++ b/packages/react-dom/src/events/__tests__/EnterLeaveEventPlugin-test.js
@@ -134,4 +134,55 @@ describe('EnterLeaveEventPlugin', () => {
     expect(childEnterCalls).toBe(1);
     expect(parentEnterCalls).toBe(0);
   });
+
+  // Test for https://github.com/facebook/react/issues/16763.
+  it('should call mouseEnter once from sibling rendered inside a rendered component', done => {
+    const mockFn = jest.fn();
+
+    class Parent extends React.Component {
+      constructor(props) {
+        super(props);
+        this.parentEl = React.createRef();
+      }
+
+      componentDidMount() {
+        ReactDOM.render(<MouseEnterDetect />, this.parentEl.current);
+      }
+
+      render() {
+        return <div ref={this.parentEl} />;
+      }
+    }
+
+    class MouseEnterDetect extends React.Component {
+      constructor(props) {
+        super(props);
+        this.firstEl = React.createRef();
+        this.siblingEl = React.createRef();
+      }
+
+      componentDidMount() {
+        this.siblingEl.current.dispatchEvent(
+          new MouseEvent('mouseout', {
+            bubbles: true,
+            cancelable: true,
+            relatedTarget: this.firstEl.current,
+          }),
+        );
+        expect(mockFn.mock.calls.length).toBe(1);
+        done();
+      }
+
+      render() {
+        return (
+          <React.Fragment>
+            <div ref={this.firstEl} onMouseEnter={mockFn} />
+            <div ref={this.siblingEl} />
+          </React.Fragment>
+        );
+      }
+    }
+
+    ReactDOM.render(<Parent />, container);
+  });
 });