Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-02 | West Virginia Wesleyan | 3 | Drake | 45 | Final | W | 42 |
| 2 | 2021-09-11 | Drake | 7 | Montana State | 45 | Final | L | -38 |
| 3 | 2021-09-18 | Drake | 0 | North Dakota | 38 | Final | L | -38 |
| 4 | 2021-09-25 | Valparaiso | 24 | Drake | 21 | Final | L | -3 |
| 5 | 2021-10-02 | Drake | 6 | Butler | 3 | Final | W | 3 |
| 6 | 2021-10-09 | Dayton | 28 | Drake | 10 | Final | L | -18 |
| 7 | 2021-10-16 | Drake | 10 | San Diego | 13 | Final | L | -3 |
| 8 | 2021-11-06 | Drake | 0 | Marist | 7 | Final | L | -7 |
| 9 | 2021-11-13 | St. Thomas | 21 | Drake | 14 | Final | L | -7 |
| 10 | 2021-11-20 | Drake | 14 | Davidson | 45 | Final | L | -31 |