| 9/2/2021 | Ohio State | 45 | at | Minnesota (9-4,6-3) | 31 | |||
| 9/11/2021 | Oregon (10-4) | 35 | at | Ohio State | 28 | P12 | ||
| 9/18/2021 | Tulsa (7-6) | 20 | at | Ohio State | 41 | AAC | ||
| 9/25/2021 | Akron (2-10) | 7 | at | Ohio State | 59 | MAC | ||
| 10/2/2021 | Ohio State | 52 | at | Rutgers (5-8,2-7) | 13 | |||
| 10/9/2021 | Maryland (7-6,3-6) | 17 | at | Ohio State | 66 | |||
| 10/23/2021 | Ohio State | 54 | at | Indiana (2-10,0-9) | 7 | |||
| 10/30/2021 | Penn State (7-6,4-5) | 24 | at | Ohio State | 33 | |||
| 11/6/2021 | Ohio State | 26 | at | Nebraska (3-9,1-8) | 17 | |||
| 11/13/2021 | Purdue (9-4,6-3) | 31 | at | Ohio State | 59 | |||
| 11/20/2021 | Michigan State (11-2,7-2) | 7 | at | Ohio State | 56 | |||
| 11/27/2021 | Ohio State | 27 | at | Michigan (12-2,9-1) | 42 | |||
| 1/1/2022 | Utah (10-4) | 45 | vs | Ohio State | 48 | Rose Bowl - Pasadena CA | P12 |
| vs Ohio State | vs Other Opponents | Ohio State compared to OOs | |
| Record: | 2-11 | 92-64 | |
| Points Scored: | 22.77 | 27.94 | 5.17 |
| Points Allowed: | 45.69 | 23.31 | 22.38 |
| Margin: | -22.92 | 4.63 | 27.55 |
| Total Points: | 68.46 | 51.25 | 17.21 |