| 9/4/2021 | Texas Tech (7-6) | 38 | at | Houston | 21 | B12 | ||
| 9/11/2021 | Houston | 44 | at | Rice (4-8) | 7 | at CUSA | ||
| 9/18/2021 | Grambling (4-7) | 0 | at | Houston | 45 | SWAC (1AA) | ||
| 9/25/2021 | Navy (4-8,3-5) | 20 | at | Houston | 28 | |||
| 10/1/2021 | Houston | 45 | at | Tulsa (7-6,5-3) | 10 | |||
| 10/7/2021 | Houston | 40 | at | Tulane (2-10,1-7) | 22 | |||
| 10/23/2021 | East Carolina (7-5,5-3) | 24 | at | Houston | 31 | OT | ||
| 10/30/2021 | SMU (8-4,4-4) | 37 | at | Houston | 44 | |||
| 11/6/2021 | Houston | 54 | at | South Florida (2-10,1-7) | 42 | |||
| 11/13/2021 | Houston | 37 | at | Temple (3-9,1-7) | 8 | |||
| 11/19/2021 | Memphis (6-6,3-5) | 13 | at | Houston | 31 | |||
| 11/27/2021 | Houston | 45 | at | Connecticut (1-11) | 17 | at Ind | ||
| 12/4/2021 | Houston | 20 | at | Cincinnati (13-1,9-0) | 35 | AAC Championship | ||
| 12/28/2021 | Houston | 17 | vs | Auburn (6-7) | 13 | Birmingham Bowl - Birmingham AL | vs SEC |
| vs Houston | vs Other Opponents | Houston compared to OOs | |
| Record: | 2-12 | 72-86 | |
| Points Scored: | 20.43 | 26.54 | 6.11 |
| Points Allowed: | 35.86 | 28.96 | 6.90 |
| Margin: | -15.43 | -2.42 | 13.01 |
| Total Points: | 56.29 | 55.50 | 0.79 |