| 9/11/2021 | DePauw | 24 | at | Butler (3-8) | 49 | at Pio | ||
| 9/18/2021 | Kenyon (3-7,3-6) | 0 | at | DePauw | 44 | |||
| 9/25/2021 | DePauw | 34 | at | Wooster (6-4,5-4) | 30 | |||
| 10/2/2021 | Hiram (1-9,0-9) | 7 | at | DePauw | 57 | |||
| 10/9/2021 | DePauw | 17 | at | Wittenberg (7-3,7-2) | 14 | |||
| 10/16/2021 | Ohio Wesleyan (8-2,7-2) | 7 | at | DePauw | 24 | |||
| 10/23/2021 | DePauw | 38 | at | Allegheny (3-7,2-7) | 14 | |||
| 10/30/2021 | Denison (6-4,6-3) | 10 | at | DePauw | 27 | |||
| 11/6/2021 | Oberlin (1-9,1-8) | 13 | at | DePauw | 66 | |||
| 11/13/2021 | DePauw | 35 | at | Wabash (7-3,6-3) | 42 | |||
| 11/20/2021 | Rose-Hulman (8-3) | 21 | at | DePauw | 26 | HCA | ||
| 11/27/2021 | DePauw | 0 | at | Wisconsin-Whitewater (13-1) | 45 | at WIAC |
| vs DePauw | vs Other Opponents | DePauw compared to OOs | |
| Record: | 3-9 | 63-51 | |
| Points Scored: | 21.00 | 31.66 | 10.66 |
| Points Allowed: | 32.67 | 27.55 | 5.12 |
| Margin: | -11.67 | 4.11 | 15.78 |
| Total Points: | 53.67 | 59.21 | -5.54 |