| 9/4/2021 | Syracuse (5-7) | 29 | at | Ohio | 9 | ACC | ||
| 9/11/2021 | Duquesne (7-3) | 28 | at | Ohio | 26 | NE (1AA) | ||
| 9/16/2021 | Ohio | 14 | at | UL Lafayette (13-1) | 49 | at SBC | ||
| 9/25/2021 | Ohio | 6 | at | Northwestern (3-9) | 35 | at B10 | ||
| 10/2/2021 | Ohio | 34 | at | Akron (2-10,1-7) | 17 | |||
| 10/9/2021 | Central Michigan (9-4,6-2) | 30 | at | Ohio | 27 | |||
| 10/16/2021 | Ohio | 26 | at | Buffalo (4-8,2-6) | 27 | |||
| 10/23/2021 | Kent State (7-7,6-3) | 34 | at | Ohio | 27 | |||
| 11/2/2021 | Miami-Ohio (7-6,5-3) | 33 | at | Ohio | 35 | |||
| 11/9/2021 | Ohio | 34 | at | Eastern Michigan (7-6,4-4) | 26 | |||
| 11/16/2021 | Toledo (7-6,5-3) | 35 | at | Ohio | 23 | |||
| 11/26/2021 | Ohio | 10 | at | Bowling Green (4-8,2-6) | 21 |
| vs Ohio | vs Other Opponents | Ohio compared to OOs | |
| Record: | 9-3 | 66-72 | |
| Points Scored: | 30.33 | 27.49 | -2.84 |
| Points Allowed: | 22.58 | 28.25 | -5.67 |
| Margin: | 7.75 | -0.76 | -8.51 |
| Total Points: | 52.91 | 55.74 | -2.83 |