| 9/4/2021 | Miami-Ohio (7-6) | 14 | at | Cincinnati | 49 | MAC | ||
| 9/11/2021 | Murray State (6-5) | 7 | at | Cincinnati | 42 | OVC (1AA) | ||
| 9/18/2021 | Cincinnati | 38 | at | Indiana (2-10) | 24 | at B10 | ||
| 10/2/2021 | Cincinnati | 24 | at | Notre Dame (11-2) | 13 | at ND | ||
| 10/8/2021 | Temple (3-9,1-7) | 3 | at | Cincinnati | 52 | |||
| 10/16/2021 | UCF (9-4,5-3) | 21 | at | Cincinnati | 56 | |||
| 10/23/2021 | Cincinnati | 27 | at | Navy (4-8,3-5) | 20 | |||
| 10/30/2021 | Cincinnati | 31 | at | Tulane (2-10,1-7) | 12 | |||
| 11/6/2021 | Tulsa (7-6,5-3) | 20 | at | Cincinnati | 28 | |||
| 11/12/2021 | Cincinnati | 45 | at | South Florida (2-10,1-7) | 28 | |||
| 11/20/2021 | SMU (8-4,4-4) | 14 | at | Cincinnati | 48 | |||
| 11/26/2021 | Cincinnati | 35 | at | East Carolina (7-5,5-3) | 13 | |||
| 12/4/2021 | Houston (12-2,8-1) | 20 | at | Cincinnati | 35 | AAC Championship | ||
| 12/31/2021 | Cincinnati | 6 | vs | Alabama (13-2) | 27 | FBS Semifinal - Arlngton TX | vs SEC |
| vs Cincinnati | vs Other Opponents | Cincinnati compared to OOs | |
| Record: | 1-13 | 92-70 | |
| Points Scored: | 16.86 | 29.40 | 12.54 |
| Points Allowed: | 36.86 | 26.17 | 10.69 |
| Margin: | -20.00 | 3.23 | 23.23 |
| Total Points: | 53.72 | 55.57 | -1.85 |