| 9/4/2021 | Southern Miss (3-9) | 7 | at | South Alabama | 31 | CUSA | ||
| 9/11/2021 | South Alabama | 22 | at | Bowling Green (4-8) | 19 | at MAC | ||
| 9/18/2021 | Alcorn State (6-5) | 21 | at | South Alabama | 28 | SWAC (1AA) | ||
| 10/2/2021 | UL Lafayette (13-1,9-0) | 20 | at | South Alabama | 18 | |||
| 10/9/2021 | South Alabama | 31 | at | Texas State (4-8,3-5) | 33 | 4OT | ||
| 10/14/2021 | Georgia Southern (3-9,2-6) | 14 | at | South Alabama | 41 | |||
| 10/23/2021 | South Alabama | 31 | at | UL Monroe (4-8,2-6) | 41 | |||
| 10/30/2021 | Arkansas State (2-10,1-7) | 13 | at | South Alabama | 31 | |||
| 11/6/2021 | South Alabama | 24 | at | Troy (5-7,3-5) | 31 | |||
| 11/13/2021 | South Alabama | 7 | at | Appalachian State (10-4,7-2) | 31 | |||
| 11/20/2021 | South Alabama | 14 | at | Tennessee (7-6) | 60 | at SEC | ||
| 11/26/2021 | Coastal Carolina (11-2,6-2) | 27 | at | South Alabama | 21 | OT |
| vs South Alabama | vs Other Opponents | South Alabama compared to OOs | |
| Record: | 7-5 | 65-72 | |
| Points Scored: | 26.42 | 27.35 | 0.93 |
| Points Allowed: | 24.92 | 28.23 | -3.31 |
| Margin: | 1.50 | -0.88 | -2.38 |
| Total Points: | 51.34 | 55.58 | -4.24 |