diff --git a/packages/@react-aria/autocomplete/src/useAutocomplete.ts b/packages/@react-aria/autocomplete/src/useAutocomplete.ts
index b569b4b6c46..7f895a676b1 100644
--- a/packages/@react-aria/autocomplete/src/useAutocomplete.ts
+++ b/packages/@react-aria/autocomplete/src/useAutocomplete.ts
@@ -124,7 +124,11 @@ export function useAutocomplete<T>(props: AriaAutocompleteOptions<T>, state: Aut
         queuedActiveDescendant.current = target.id;
         state.setFocusedNodeId(target.id);
       }
-    } else {
+    } else if (queuedActiveDescendant.current && !document.getElementById(queuedActiveDescendant.current)) {
+      // If we recieve a focus event refocusing the collection, either we have newly refocused the input and are waiting for the
+      // wrapped collection to refocus the previously focused node if any OR
+      // we are in a state where we've filtered to such a point that there aren't any matching items in the collection to focus.
+      // In this case we want to clear tracked item if any and clear active descendant
       queuedActiveDescendant.current = null;
       state.setFocusedNodeId(null);
     }
@@ -189,7 +193,7 @@ export function useAutocomplete<T>(props: AriaAutocompleteOptions<T>, state: Aut
     // copy paste/backspacing/undo/redo for screen reader announcements
     if (lastInputType.current === 'insertText' && !disableAutoFocusFirst) {
       focusFirstItem();
-    } else if (lastInputType.current.includes('insert') || lastInputType.current.includes('delete') || lastInputType.current.includes('history')) {
+    } else if (lastInputType.current && (lastInputType.current.includes('insert') || lastInputType.current.includes('delete') || lastInputType.current.includes('history'))) {
       clearVirtualFocus(true);
 
       // If onChange was triggered before the timeout actually updated the activedescendant, we need to fire
@@ -274,9 +278,11 @@ export function useAutocomplete<T>(props: AriaAutocompleteOptions<T>, state: Aut
         ) || false;
       } else {
         let item = document.getElementById(focusedNodeId);
-        shouldPerformDefaultAction = item?.dispatchEvent(
-          new KeyboardEvent(e.nativeEvent.type, e.nativeEvent)
-        ) || false;
+        if (item) {
+          shouldPerformDefaultAction = item?.dispatchEvent(
+            new KeyboardEvent(e.nativeEvent.type, e.nativeEvent)
+          ) || false;
+        }
       }
     }
 
@@ -366,8 +372,9 @@ export function useAutocomplete<T>(props: AriaAutocompleteOptions<T>, state: Aut
     if (curFocusedNode) {
       let target = e.target;
       queueMicrotask(() => {
-        dispatchVirtualBlur(target, curFocusedNode);
-        dispatchVirtualFocus(curFocusedNode, target);
+        // instead of focusing the last focused node, just focus the collection instead and have the collection handle what item to focus via useSelectableCollection/Item
+        dispatchVirtualBlur(target, collectionRef.current);
+        dispatchVirtualFocus(collectionRef.current!, target);
       });
     }
   };
diff --git a/packages/react-aria-components/test/Autocomplete.test.tsx b/packages/react-aria-components/test/Autocomplete.test.tsx
index 1322e3940a1..20eaeaaf0a3 100644
--- a/packages/react-aria-components/test/Autocomplete.test.tsx
+++ b/packages/react-aria-components/test/Autocomplete.test.tsx
@@ -12,8 +12,8 @@
 
 import {act, pointerMap, render, within} from '@react-spectrum/test-utils-internal';
 import {AriaAutocompleteTests} from './AriaAutocomplete.test-util';
-import {Autocomplete, Breadcrumb, Breadcrumbs, Button, Cell, Column, Dialog, DialogTrigger, GridList, GridListItem, Header, Input, Label, ListBox, ListBoxItem, ListBoxSection, Menu, MenuItem, MenuSection, Popover, Row, SearchField, Select, SelectValue, Separator, SubmenuTrigger, Tab, Table, TableBody, TableHeader, TabList, TabPanel, Tabs, Tag, TagGroup, TagList, Text, TextField, Tree, TreeItem, TreeItemContent} from '..';
-import React, {ReactNode} from 'react';
+import {Autocomplete, Breadcrumb, Breadcrumbs, Button, Cell, Collection, Column, Dialog, DialogTrigger, GridList, GridListItem, Header, Input, Label, ListBox, ListBoxItem, ListBoxLoadMoreItem, ListBoxSection, Menu, MenuItem, MenuSection, Popover, Row, SearchField, Select, SelectValue, Separator, SubmenuTrigger, Tab, Table, TableBody, TableHeader, TabList, TabPanel, Tabs, Tag, TagGroup, TagList, Text, TextField, Tree, TreeItem, TreeItemContent} from '..';
+import React, {ReactNode, useEffect, useState} from 'react';
 import {useAsyncList} from 'react-stately';
 import {useFilter} from '@react-aria/i18n';
 import userEvent from '@testing-library/user-event';
@@ -957,6 +957,73 @@ describe('Autocomplete', () => {
     expect(within(sections[0]).getByText('Baz')).toBeTruthy();
     expect(within(sections[1]).getByText('Copy')).toBeTruthy();
   });
+
+
+  it('shouldnt prevent default on keyboard interactions if somehow the active descendant doesnt exist in the DOM', async () => {
+    let defaultOptions = [
+      {value: 'one'},
+      {value: 'two'},
+      {value: 'three'},
+      {value: 'four'},
+      {value: 'five'}
+    ];
+    function ControlledItemsFilter() {
+      const [options, setOptions] = useState(defaultOptions);
+      const [inputValue, onInputChange] = useState('');
+
+      useEffect(() => {
+        setOptions(
+          defaultOptions.filter(({value}) => value.includes(inputValue))
+        );
+      }, [inputValue]);
+
+      return (
+        <Autocomplete inputValue={inputValue} onInputChange={onInputChange}>
+          <SearchField aria-label="Search">
+            <Input aria-label="Search" placeholder="Search..." />
+            <Button>X</Button>
+          </SearchField>
+          <ListBox selectionMode="multiple">
+            <Collection items={options} dependencies={[inputValue]}>
+              {(option) => (
+                <ListBoxItem id={option.value}>{option.value}</ListBoxItem>
+              )}
+            </Collection>
+            <ListBoxLoadMoreItem onLoadMore={() => {}} isLoading={false}>
+              <div>Loading...</div>
+            </ListBoxLoadMoreItem>
+          </ListBox>
+        </Autocomplete>
+      );
+    }
+    let {getByRole} = render(
+      <ControlledItemsFilter />
+    );
+
+    let input = getByRole('searchbox');
+    await user.tab();
+    expect(document.activeElement).toBe(input);
+    await user.keyboard('o');
+    act(() => jest.runAllTimers());
+    let listbox = getByRole('listbox');
+    let options = within(listbox).getAllByRole('option');
+    expect(options).toHaveLength(3);
+    expect(input).toHaveAttribute('aria-activedescendant', options[0].id);
+
+    await user.keyboard('o');
+    act(() => jest.runAllTimers());
+    options = within(listbox).queryAllByRole('option');
+    expect(options).toHaveLength(0);
+    // TODO: this is strange, still need to investigate. Ideally this would be removed
+    // but the collection in this configuration doesn't seem to update in time, so
+    // useSelectableCollection doesn't properly resend virtual focus to the input
+    expect(input).toHaveAttribute('aria-activedescendant');
+
+    await user.keyboard('{Backspace}');
+    act(() => jest.runAllTimers());
+    options = within(listbox).getAllByRole('option');
+    expect(options).toHaveLength(3);
+  });
 });
 
 AriaAutocompleteTests({