| 9/2/2021 | West Virginia Wesleyan (0-10) | 3 | at | Drake | 45 | MtnE (D2) | ||
| 9/11/2021 | Drake | 7 | at | Montana State (12-3) | 45 | at BSky | ||
| 9/18/2021 | Drake | 0 | at | North Dakota (5-6) | 38 | at MVC | ||
| 9/25/2021 | Valparaiso (4-7,4-4) | 24 | at | Drake | 21 | |||
| 10/2/2021 | Drake | 6 | at | Butler (3-8,1-7) | 3 | |||
| 10/9/2021 | Dayton (6-4,5-3) | 28 | at | Drake | 10 | |||
| 10/16/2021 | Drake | 10 | at | San Diego (7-4,7-1) | 13 | |||
| 10/23/2021 | Stetson (3-7,1-6) | vs | Drake | Cancelled COVID | ||||
| 11/6/2021 | Drake | 0 | at | Marist (5-5,5-3) | 7 | |||
| 11/13/2021 | St Thomas (7-3,6-2) | 21 | at | Drake | 14 | |||
| 11/20/2021 | Drake | 14 | at | Davidson (8-3,7-1) | 45 |
| vs Drake | vs Other Opponents | Drake compared to OOs | |
| Record: | 8-2 | 52-58 | |
| Points Scored: | 22.70 | 26.03 | 3.33 |
| Points Allowed: | 12.70 | 28.25 | -15.55 |
| Margin: | 10.00 | -2.22 | -12.22 |
| Total Points: | 35.40 | 54.28 | -18.88 |