| 9/3/2021 | Hobart | 35 | at | Alfred | 3 | @ E8 | ||
| 9/4/2021 | St Lawrence | 14 | at | Endicott | 27 | @ CCF | ||
| Bridgewater State MA | 20 | at | Ithaca | 52 | MSCAC | |||
| Case Western Reserve | 27 | at | Rochester | 20 | TPAC | |||
| Montclair State | 20 | at | Rensselaer | 21 | NJAC | |||
| Morrisville | 14 | at | Union NY | 48 | E8 | |||
| 9/11/2021 | Ithaca | 23 | at | Brockport State | 8 | @ E8 | ||
| Morrisville | 0 | at | Hobart | 41 | E8 | |||
| Alfred State | 27 | at | Rochester | 28 | ECFC | |||
| Stevenson | 10 | at | Rensselaer | 14 | MidAC | |||
| Norwich | 7 | at | St Lawrence | 37 | NEWMAC | |||
| Union NY | 62 | at | Worcester State | 13 | @ MSCAC | |||
| 9/17/2021 | St Lawrence | 27 | at | Morrisville | 14 | @ E8 | ||
| 9/18/2021 | Ithaca | 34 | at | Alfred | 0 | @ E8 | ||
| Rochester | 7 | at | Brockport State | 16 | @ E8 | |||
| Hobart | 42 | at | St John Fisher | 21 | @ E8 | |||
| Springfield | 23 | at | Union NY | 30 | NEWMAC | |||
| Rensselaer | 24 | at | Worcester Polytechnic | 10 | @ NEWMAC | |||
| 9/25/2021 | Keystone | 14 | at | Hobart | 58 | ECFC | ||
| St John Fisher | 7 | at | Rensselaer | 41 | E8 | |||
| Castleton State | 3 | at | St Lawrence | 55 | ECFC | |||
| Union NY | 30 | at | Utica | 9 | @ E8 | |||
| 10/2/2021 | Union NY | 30 | at | Buffalo State | 17 | @ E8 | ||
| Hobart | 21 | at | Ithaca | 28 | ||||
| Rochester | 22 | at | Rensselaer | 38 | ||||
| 10/9/2021 | Ithaca | 37 | at | Rochester | 14 | |||
| Buffalo State | 16 | at | Rensselaer | 24 | E8 | |||
| St Lawrence | 7 | at | Union NY | 37 | ||||
| 10/16/2021 | Rochester | 14 | at | Buffalo State | 7 | @ E8 | ||
| Rensselaer | 9 | at | Hobart | 10 | ||||
| Ithaca | 17 | at | St Lawrence | 0 | ||||
| 10/23/2021 | St Lawrence | 13 | at | Hobart | 17 | |||
| Buffalo State | 7 | at | Ithaca | 51 | E8 | |||
| Union NY | 35 | at | Rochester | 9 | ||||
| 10/30/2021 | Ithaca | 11 | at | Rensselaer | 14 | |||
| Rochester | 10 | at | St Lawrence | 34 | ||||
| Hobart | 20 | at | Union NY | 27 | OT | |||
| 11/6/2021 | Rochester | 42 | at | Hartwick | 28 | @ E8 | ||
| Buffalo State | 21 | at | Hobart | 45 | E8 | |||
| Union NY | 7 | at | Ithaca | 26 | ||||
| Rensselaer | 22 | at | St Lawrence | 20 | 2OT | |||
| 11/13/2021 | St Lawrence | 41 | at | Buffalo State | 6 | @ E8 | ||
| Ithaca | 27 | at | Cortland | 28 | @ E8 | |||
| Hobart | 31 | at | Rochester | 0 | ||||
| Rensselaer | 19 | at | Union NY | 17 | ||||
| 11/20/2021 | Rensselaer | 20 | at | Endicott | 14 | @ CCF | ||
| Hobart | 21 | at | Westminster PA | 3 | @ TPAC | |||
| 11/27/2021 | Rensselaer | 21 | at | Cortland | 14 | @ E8 | ||
| 12/4/2021 | Rensselaer | 6 | at | North Central | 55 | @ CCIW |