| 9/2/2021 | Shepherd (13-2) | 35 | at | Ohio Dominican | 30 | PSAC | ||
| 9/11/2021 | Virginia State (3-6) | 7 | at | Ohio Dominican | 10 | CIAA | ||
| 9/18/2021 | Ohio Dominican | 35 | at | William Jewell (0-11) | 25 | at GLV | ||
| 9/25/2021 | Ohio Dominican | 19 | at | Indianapolis (7-4) | 16 | at GLV | ||
| 10/2/2021 | Ohio Dominican | 32 | at | Kentucky Wesleyan (3-8,1-6) | 30 | |||
| 10/9/2021 | Ohio Dominican | 34 | at | Ashland (5-5,4-3) | 24 | |||
| 10/16/2021 | Findlay (8-4,6-1) | 21 | at | Ohio Dominican | 14 | |||
| 10/23/2021 | Walsh (2-9,1-6) | 17 | at | Ohio Dominican | 56 | |||
| 10/30/2021 | Ohio Dominican | 21 | at | Tiffin (8-3,5-2) | 34 | |||
| 11/6/2021 | Lake Erie (5-6,2-5) | 0 | at | Ohio Dominican | 31 | |||
| 11/13/2021 | Ohio Dominican | 17 | at | Hillsdale (6-6,5-2) | 21 |
| vs Ohio Dominican | vs Other Opponents | Ohio Dominican compared to OOs | |
| Record: | 4-7 | 56-57 | |
| Points Scored: | 20.91 | 27.81 | 6.90 |
| Points Allowed: | 27.18 | 26.85 | 0.33 |
| Margin: | -6.27 | 0.96 | 7.23 |
| Total Points: | 48.09 | 54.66 | -6.57 |