| Rk | Gcar | Gtm | Date | School | Opponent | Type | Result | |
|---|---|---|---|---|---|---|---|---|
| 1 | 1 | 1 | 2021-09-02 | Buffalo | Wagner | REG (Non-Conf) | W 69-7 | |
| 2 | 2 | 2 | 2021-09-11 | Buffalo | @ | Nebraska | REG (Non-Conf) | L 3-28 |
| 3 | 3 | 3 | 2021-09-18 | Buffalo | Coastal Carolina | REG (Non-Conf) | L 25-28 | |
| 4 | 4 | 4 | 2021-09-25 | Buffalo | @ | Old Dominion | REG (Non-Conf) | W 35-34 |
| 5 | 5 | 5 | 2021-10-02 | Buffalo | Western Michigan | REG (Conf) | L 17-24 | |
| 6 | 6 | 6 | 2021-10-09 | Buffalo | @ | Kent State | REG (Conf) | L 38-48 |
| 7 | 7 | 7 | 2021-10-16 | Buffalo | Ohio | REG (Conf) | W 27-26 | |
| 8 | 8 | 8 | 2021-10-23 | Buffalo | @ | Akron | REG (Conf) | W 45-10 |
| 9 | 9 | 9 | 2021-10-30 | Buffalo | Bowling Green | REG (Conf) | L 44-56 | |
| 10 | 10 | 10 | 2021-11-09 | Buffalo | @ | Miami (OH) | REG (Conf) | L 18-45 |
| 11 | 11 | 11 | 2021-11-17 | Buffalo | Northern Illinois | REG (Conf) | L 27-33 | |
| 12 | 12 | 12 | 2021-11-23 | Buffalo | @ | Ball State | REG (Conf) | L 3-20 |
| 4-8 |
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