Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Prairie View A&M | 40 | Texas Southern | 17 | Final | L | -23 |
| 2 | 2021-09-11 | Texas Southern | 7 | Baylor | 66 | Final | L | -59 |
| 3 | 2021-09-25 | Texas Southern | 34 | Rice | 48 | Final | L | -14 |
| 4 | 2021-10-09 | Texas Southern | 35 | Southern | 31 | Final | W | 4 |
| 5 | 2021-10-16 | Texas Southern | 20 | Grambling | 34 | Final | L | -14 |
| 6 | 2021-10-23 | Alcorn State | 44 | Texas Southern | 27 | Final | L | -17 |
| 7 | 2021-10-30 | Arkansas-Pine Bluff | 17 | Texas Southern | 59 | Final | W | 42 |
| 8 | 2021-11-06 | Texas Southern | 21 | Jackson State | 41 | Final | L | -20 |
| 9 | 2021-11-13 | Alabama A&M | 52 | Texas Southern | 49 | Final | L | -3 |
| 10 | 2021-11-20 | Texas Southern | 21 | Alabama State | 24 | Final | L | -3 |