| Champ: |  Garbiñe Muguruza |
| Runner: |  Ons Jabeur |
| Score: | 3–6, 6–3, 6–0 |
| Draw: | 56 |
| Seeds: | 16 |
| Type: | singles doubles |
| Edition: | 1st |
| After Name: | Chicago Fall Tennis Classic – Singles |
See main article: article and 2021 Chicago Fall Tennis Classic.
This was the first edition of the event.
Garbiñe Muguruza won the title, defeating Ons Jabeur in the final, 3–6, 6–3, 6–0.
The top eight seeds received a bye into the second round.