Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Nicholls State | 17 | Memphis | 42 | Final | L | -25 |
| 2 | 2021-09-11 | Nicholls State | 24 | Louisiana | 27 | Final | L | -3 |
| 3 | 2021-09-25 | North Alabama | 14 | Nicholls State | 31 | Final | W | 17 |
| 4 | 2021-10-02 | Houston Baptist | 17 | Nicholls State | 48 | Final | W | 31 |
| 5 | 2021-10-09 | Southeastern Louisiana | 58 | Nicholls State | 48 | Final | L | -10 |
| 6 | 2021-10-16 | Nicholls State | 21 | Incarnate Word | 38 | Final | L | -17 |
| 7 | 2021-10-23 | Nicholls State | 44 | Houston Baptist | 14 | Final | W | 30 |
| 8 | 2021-10-30 | Northwestern State | 21 | Nicholls State | 42 | Final | W | 21 |
| 9 | 2021-11-06 | Nicholls State | 24 | McNeese State | 14 | Final | W | 10 |
| 10 | 2021-11-13 | Incarnate Word | 27 | Nicholls State | 23 | Final | L | -4 |
| 11 | 2021-11-18 | Nicholls State | 45 | Southeastern Louisiana | 42 | Final | W | 3 |