Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Georgia | 10 | Clemson | 3 | Final | L | -7 |
| 2 | 2021-09-11 | South Carolina State | 3 | Clemson | 49 | Final | W | 46 |
| 3 | 2021-09-18 | Georgia Tech | 8 | Clemson | 14 | Final | W | 6 |
| 4 | 2021-09-25 | Clemson | 21 | North Carolina State | 27 | Final(OT) | L | -6 |
| 5 | 2021-10-02 | Boston College | 13 | Clemson | 19 | Final | W | 6 |
| 6 | 2021-10-15 | Clemson | 17 | Syracuse | 14 | Final | W | 3 |
| 7 | 2021-10-23 | Clemson | 17 | Pittsburgh | 27 | Final | L | -10 |
| 8 | 2021-10-30 | Florida State | 20 | Clemson | 30 | Final | W | 10 |
| 9 | 2021-11-06 | Clemson | 30 | Louisville | 24 | Final | W | 6 |
| 10 | 2021-11-13 | Connecticut | 7 | Clemson | 44 | Final | W | 37 |
| 11 | 2021-11-20 | Wake Forest | 27 | Clemson | 48 | Final | W | 21 |
| 12 | 2021-11-27 | Clemson (17) | 30 | South Carolina (64) | 0 | Final | W | 30 |
| 13 | 2021-12-29 | Clemson (13) | 20 | Iowa State (34) | 13 | Final | W | 7 |