Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Miami (OH) | 14 | Cincinnati | 49 | Final | W | 35 |
| 2 | 2021-09-11 | Murray State | 7 | Cincinnati | 42 | Final | W | 35 |
| 3 | 2021-09-18 | Cincinnati | 38 | Indiana | 24 | Final | W | 14 |
| 4 | 2021-10-02 | Cincinnati | 24 | Notre Dame | 13 | Final | W | 11 |
| 5 | 2021-10-08 | Temple | 3 | Cincinnati | 52 | Final | W | 49 |
| 6 | 2021-10-16 | Central Florida | 21 | Cincinnati | 56 | Final | W | 35 |
| 7 | 2021-10-23 | Cincinnati | 27 | Navy | 20 | Final | W | 7 |
| 8 | 2021-10-30 | Cincinnati | 31 | Tulane | 12 | Final | W | 19 |
| 9 | 2021-11-06 | Tulsa | 20 | Cincinnati | 28 | Final | W | 8 |
| 10 | 2021-11-12 | Cincinnati | 45 | South Florida | 28 | Final | W | 17 |
| 11 | 2021-11-20 | SMU | 14 | Cincinnati | 48 | Final | W | 34 |
| 12 | 2021-11-26 | Cincinnati (2) | 35 | East Carolina (61) | 13 | Final | W | 22 |
| 13 | 2021-12-04 | Houston (22) | 20 | Cincinnati (2) | 35 | Final | W | 15 |
| 14 | 2021-12-31 | Cincinnati (5) | 6 | Alabama (2) | 27 | Final | L | -21 |