diff --git a/src/cdk/a11y/fake-event-detection.ts b/src/cdk/a11y/fake-event-detection.ts
index 6835b6885c49..b5fe69c52003 100644
--- a/src/cdk/a11y/fake-event-detection.ts
+++ b/src/cdk/a11y/fake-event-detection.ts
@@ -8,11 +8,12 @@
 
 /** Gets whether an event could be a faked `mousedown` event dispatched by a screen reader. */
 export function isFakeMousedownFromScreenReader(event: MouseEvent): boolean {
-  // We can typically distinguish between these faked mousedown events and real mousedown events
-  // using the "buttons" property. While real mousedowns will indicate the mouse button that was
-  // pressed (e.g. "1" for the left mouse button), faked mousedowns will usually set the property
-  // value to 0.
-  return event.buttons === 0;
+  // Some screen readers will dispatch a fake `mousedown` event when pressing enter or space on
+  // a clickable element. We can distinguish these events when both `offsetX` and `offsetY` are
+  // zero. Note that there's an edge case where the user could click the 0x0 spot of the screen
+  // themselves, but that is unlikely to contain interaction elements. Historially we used to check
+  // `event.buttons === 0`, however that no longer works on recent versions of NVDA.
+  return event.offsetX === 0 && event.offsetY === 0;
 }
 
 /** Gets whether an event could be a faked `touchstart` event dispatched by a screen reader. */
diff --git a/src/cdk/a11y/focus-monitor/focus-monitor.spec.ts b/src/cdk/a11y/focus-monitor/focus-monitor.spec.ts
index 09a3f71ed27e..11708fd777c4 100644
--- a/src/cdk/a11y/focus-monitor/focus-monitor.spec.ts
+++ b/src/cdk/a11y/focus-monitor/focus-monitor.spec.ts
@@ -151,7 +151,7 @@ describe('FocusMonitor', () => {
     // Simulate focus via a fake mousedown from a screen reader.
     dispatchMouseEvent(buttonElement, 'mousedown');
     const event = createMouseEvent('mousedown');
-    Object.defineProperty(event, 'buttons', {get: () => 0});
+    Object.defineProperties(event, {offsetX: {get: () => 0}, offsetY: {get: () => 0}});
     dispatchEvent(buttonElement, event);
 
     buttonElement.focus();
diff --git a/src/cdk/a11y/input-modality/input-modality-detector.spec.ts b/src/cdk/a11y/input-modality/input-modality-detector.spec.ts
index f379ca8f6b53..c83501b1b696 100644
--- a/src/cdk/a11y/input-modality/input-modality-detector.spec.ts
+++ b/src/cdk/a11y/input-modality/input-modality-detector.spec.ts
@@ -134,7 +134,7 @@ describe('InputModalityDetector', () => {
 
     // Create a fake screen-reader mouse event.
     const event = createMouseEvent('mousedown');
-    Object.defineProperty(event, 'buttons', {get: () => 0});
+    Object.defineProperties(event, {offsetX: {get: () => 0}, offsetY: {get: () => 0}});
     dispatchEvent(document, event);
 
     expect(detector.mostRecentModality).toBe('keyboard');
diff --git a/src/cdk/testing/testbed/fake-events/event-objects.ts b/src/cdk/testing/testbed/fake-events/event-objects.ts
index 63687ab94560..a4a065280b33 100644
--- a/src/cdk/testing/testbed/fake-events/event-objects.ts
+++ b/src/cdk/testing/testbed/fake-events/event-objects.ts
@@ -43,9 +43,11 @@ export function createMouseEvent(
     /* button */ button,
     /* relatedTarget */ null);
 
-  // `initMouseEvent` doesn't allow us to pass the `buttons` and
-  // defaults it to 0 which looks like a fake event.
+  // `initMouseEvent` doesn't allow us to pass these properties into the constructor.
+  // Override them to 1, because they're used for fake screen reader event detection.
   defineReadonlyEventProperty(event, 'buttons', 1);
+  defineReadonlyEventProperty(event, 'offsetX', 1);
+  defineReadonlyEventProperty(event, 'offsetY', 1);
 
   // IE won't set `defaultPrevented` on synthetic events so we need to do it manually.
   event.preventDefault = function() {
diff --git a/src/material/core/ripple/ripple.spec.ts b/src/material/core/ripple/ripple.spec.ts
index 2bb554392b25..22a643a60522 100644
--- a/src/material/core/ripple/ripple.spec.ts
+++ b/src/material/core/ripple/ripple.spec.ts
@@ -181,7 +181,7 @@ describe('MatRipple', () => {
 
     it('should ignore fake mouse events from screen readers', fakeAsync(() => {
       const event = createMouseEvent('mousedown');
-      Object.defineProperty(event, 'buttons', {get: () => 0});
+      Object.defineProperties(event, {offsetX: {get: () => 0}, offsetY: {get: () => 0}});
 
       dispatchEvent(rippleTarget, event);
       tick(enterDuration);