diff --git a/.changeset/autocomplete-blur-suggestion.md b/.changeset/autocomplete-blur-suggestion.md
new file mode 100644
index 00000000000..f05c0a4c428
--- /dev/null
+++ b/.changeset/autocomplete-blur-suggestion.md
@@ -0,0 +1,5 @@
+---
+'@primer/react': patch
+---
+
+Autocomplete: Keep the typed text instead of restoring the full inline suggestion when the input loses focus, matching the behavior of pressing Escape
diff --git a/packages/react/src/Autocomplete/Autocomplete.test.tsx b/packages/react/src/Autocomplete/Autocomplete.test.tsx
index 68e61313b3e..ab1d46a7e6d 100644
--- a/packages/react/src/Autocomplete/Autocomplete.test.tsx
+++ b/packages/react/src/Autocomplete/Autocomplete.test.tsx
@@ -214,6 +214,30 @@ describe('Autocomplete', () => {
       expect(inputNode?.getAttribute('aria-expanded')).not.toBe('true')
     })
 
+    it('does not restore the autocomplete suggestion when the input is blurred', async () => {
+      const user = userEvent.setup()
+      const {container} = render(
+        <>
+          <LabelledAutocomplete
+            menuProps={{items: mockItems, selectedItemIds: [], ['aria-labelledby']: 'autocompleteLabel'}}
+          />
+          <button type="button">outside</button>
+        </>,
+      )
+      const inputNode = container.querySelector('#autocompleteInput') as HTMLInputElement
+      const outsideButton = screen.getByRole('button', {name: 'outside'})
+
+      // Type 'ze' which gets the inline autocomplete suggestion 'zero'
+      await user.type(inputNode, 'ze')
+      expect(inputNode.value).toBe('zero')
+
+      // Move focus elsewhere on the page, like clicking outside the Autocomplete
+      await user.click(outsideButton)
+
+      // The input should retain the text the user typed rather than the full suggestion
+      await waitFor(() => expect(inputNode.value).toBe('ze'))
+    })
+
     it('allows the value to be 0', () => {
       const {getByDisplayValue} = render(
         <LabelledAutocomplete
diff --git a/packages/react/src/Autocomplete/AutocompleteInput.tsx b/packages/react/src/Autocomplete/AutocompleteInput.tsx
index ef1278451a1..735b98cb5c1 100644
--- a/packages/react/src/Autocomplete/AutocompleteInput.tsx
+++ b/packages/react/src/Autocomplete/AutocompleteInput.tsx
@@ -64,10 +64,18 @@ const AutocompleteInput = React.forwardRef(
         safeSetTimeout(() => {
           if (document.activeElement !== inputRef.current) {
             setShowMenu(false)
+
+            // Reset the input's value to the text the user actually typed rather than leaving the
+            // inline autocomplete suggestion in place. This keeps the blur behavior consistent with
+            // pressing Escape, so deleting characters off a selection and then clicking away does not
+            // silently restore the full suggestion. See https://github.com/primer/react/issues/4275
+            if (inputRef.current && autocompleteSuggestion && inputRef.current.value !== inputValue) {
+              inputRef.current.value = inputValue
+            }
           }
         }, 0)
       },
-      [onBlur, setShowMenu, inputRef, safeSetTimeout],
+      [onBlur, setShowMenu, inputRef, safeSetTimeout, autocompleteSuggestion, inputValue],
     )
 
     const handleInputChange: ChangeEventHandler<HTMLInputElement> = event => {
@@ -136,7 +144,17 @@ const AutocompleteInput = React.forwardRef(
       // TODO: fix bug where this function prevents `onChange` from being triggered if the highlighted item text
       //       is the same as what I'm typing
       //       e.g.: typing 'tw' highlights 'two', but when I 'two', the text input change does not get triggered
-      if (highlightRemainingText && autocompleteSuggestion && (inputValue || isMenuDirectlyActivated)) {
+      // Only apply the inline autocomplete suggestion while the input is focused. Without this guard,
+      // the suggestion can be re-applied to the DOM after the input is blurred, which would restore
+      // the full suggestion the user was editing away from. See https://github.com/primer/react/issues/4275
+      const isInputFocused = document.activeElement === inputRef.current
+
+      if (
+        isInputFocused &&
+        highlightRemainingText &&
+        autocompleteSuggestion &&
+        (inputValue || isMenuDirectlyActivated)
+      ) {
         inputRef.current.value = autocompleteSuggestion
 
         if (autocompleteSuggestion.toLowerCase().indexOf(inputValue.toLowerCase()) === 0) {