| 9/4/2021 | Case Western Reserve (6-4) | 27 | at | Rochester | 20 | TPAC | ||
| 9/11/2021 | Alfred State (6-5) | 27 | at | Rochester | 28 | ECFC | ||
| 9/18/2021 | Rochester | 7 | at | Brockport State (8-3) | 16 | at E8 | ||
| 10/2/2021 | Rochester | 22 | at | Rensselaer (11-2,4-1) | 38 | |||
| 10/9/2021 | Ithaca (8-2,4-1) | 37 | at | Rochester | 14 | |||
| 10/16/2021 | Rochester | 14 | at | Buffalo State (0-10) | 7 | at E8 | ||
| 10/23/2021 | Union NY (8-2,3-2) | 35 | at | Rochester | 9 | |||
| 10/30/2021 | Rochester | 10 | at | St Lawrence (5-5,1-4) | 34 | |||
| 11/6/2021 | Rochester | 42 | at | Hartwick (2-7) | 28 | at E8 | ||
| 11/13/2021 | Hobart (9-2,3-2) | 31 | at | Rochester | 0 |
| vs Rochester | vs Other Opponents | Rochester compared to OOs | |
| Record: | 7-3 | 56-39 | |
| Points Scored: | 28.00 | 24.84 | -3.16 |
| Points Allowed: | 16.60 | 20.00 | -3.40 |
| Margin: | 11.40 | 4.84 | -6.56 |
| Total Points: | 44.60 | 44.84 | -0.24 |