| Date | Home | Time/Results | Away | League | Season | Venue |
|---|---|---|---|---|---|---|
Rochester Lancers  | 0 - 3 |  FC Buffalo | Regular Season | 2021m | Aquinas Institute | |
| FC Buffalo | 1 - 1 |  Syracuse FC | Regular Season | 2021m | Dobson Field | |
| FC Buffalo | 5 - 1 |  Erie Commodores FC | Regular Season | 2021m | Robert E. Rich All-High Stadium | |
Pittsburgh Hotspurs  | 2 - 0 | FC Buffalo | Regular Season | 2021m | Founders Field | |
| FC Buffalo | 1 - 2 |  Cleveland SC | Regular Season | 2021m | Robert E. Rich All-High Stadium | |
| FC Buffalo | 1 - 2 | Pittsburgh Hotspurs | Regular Season | 2021m | Robert E. Rich All-High Stadium | |
| Cleveland SC | 3 - 1 | FC Buffalo | Regular Season | 2021m | ||
| Erie Commodores FC | 1 - 1 | FC Buffalo | Regular Season | 2021m | ||
| FC Buffalo | 2 - 1 | Rochester Lancers | Regular Season | 2021m | Robert E. Rich All-High Stadium | |
Detroit City FC  | 3 - 1 | FC Buffalo | NISA Independent Cup | 2021m | Keyworth Stadium | |
| Syracuse FC | 1 - 4 | FC Buffalo | Regular Season | 2021m | Lazer Stadium at Onondaga Community College | |
| FC Buffalo | 3 - 0 |  Livonia City | NISA Independent Cup | 2021m | Dobson Field | |
| FC Buffalo | 7 - 0 | Cleveland SC | NISA Independent Cup | 2021m | Robert E. Rich All-High Stadium |
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