Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Southern Miss | 7 | South Alabama | 31 | Final | W | 24 |
| 2 | 2021-09-11 | South Alabama | 22 | Bowling Green | 19 | Final | W | 3 |
| 3 | 2021-09-18 | Alcorn State | 21 | South Alabama | 28 | Final | W | 7 |
| 4 | 2021-10-02 | Louisiana | 20 | South Alabama | 18 | Final | L | -2 |
| 5 | 2021-10-09 | South Alabama | 31 | Texas State | 33 | Final/4OT | L | -2 |
| 6 | 2021-10-10 | South Alabama | 31 | Texas State | 33 | Final(OT) | L | -2 |
| 7 | 2021-10-14 | Georgia Southern | 14 | South Alabama | 41 | Final | W | 27 |
| 8 | 2021-10-23 | South Alabama | 31 | Louisiana-Monroe | 41 | Final | L | -10 |
| 9 | 2021-10-30 | Arkansas State | 13 | South Alabama | 31 | Final | W | 18 |
| 10 | 2021-11-06 | South Alabama | 24 | Troy | 31 | Final | L | -7 |
| 11 | 2021-11-13 | South Alabama | 7 | Appalachian State | 31 | Final | L | -24 |
| 12 | 2021-11-20 | South Alabama | 14 | Tennessee | 60 | Final | L | -46 |
| 13 | 2021-11-26 | Coastal Carolina (43) | 27 | South Alabama (118) | 21 | Final(OT) | L | -6 |