Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Syracuse | 29 | Ohio | 9 | Final | W | 20 |
| 2 | 2021-09-11 | Rutgers | 17 | Syracuse | 7 | Final | L | -10 |
| 3 | 2021-09-18 | Albany | 24 | Syracuse | 62 | Final | W | 38 |
| 4 | 2021-09-24 | Liberty | 21 | Syracuse | 24 | Final | W | 3 |
| 5 | 2021-10-02 | Syracuse | 30 | Florida State | 33 | Final | L | -3 |
| 6 | 2021-10-09 | Wake Forest | 40 | Syracuse | 37 | Final(OT) | L | -3 |
| 7 | 2021-10-15 | Clemson | 17 | Syracuse | 14 | Final | L | -3 |
| 8 | 2021-10-23 | Syracuse | 41 | Virginia Tech | 36 | Final | W | 5 |
| 9 | 2021-10-30 | Boston College | 6 | Syracuse | 21 | Final | W | 15 |
| 10 | 2021-11-13 | Syracuse | 3 | Louisville | 41 | Final | L | -38 |
| 11 | 2021-11-20 | Syracuse | 17 | North Carolina State | 41 | Final | L | -24 |
| 12 | 2021-11-27 | Pittsburgh (16) | 31 | Syracuse (78) | 14 | Final | L | -17 |