| 9/4/2021 | Georgia (14-1) | 10 | vs | Clemson | 3 | Charlotte NC | SEC | |
| 9/11/2021 | South Carolina State (7-5) | 3 | at | Clemson | 49 | MEAC (1AA) | ||
| 9/18/2021 | Georgia Tech (3-9,2-6) | 8 | at | Clemson | 14 | |||
| 9/25/2021 | Clemson | 21 | at | North Carolina State (9-3,6-2) | 27 | 2OT | ||
| 10/2/2021 | Boston College (6-6,2-6) | 13 | at | Clemson | 19 | |||
| 10/15/2021 | Clemson | 17 | at | Syracuse (5-7,2-6) | 14 | |||
| 10/23/2021 | Clemson | 17 | at | Pittsburgh (11-3,8-1) | 27 | |||
| 10/30/2021 | Florida State (5-7,4-4) | 20 | at | Clemson | 30 | |||
| 11/6/2021 | Clemson | 30 | at | Louisville (6-7,4-4) | 24 | |||
| 11/13/2021 | Connecticut (1-11) | 7 | at | Clemson | 44 | Ind | ||
| 11/20/2021 | Wake Forest (11-3,7-3) | 27 | at | Clemson | 48 | |||
| 11/27/2021 | Clemson | 30 | at | South Carolina (7-6) | 0 | at SEC | ||
| 12/29/2021 | Clemson | 20 | vs | Iowa State (7-6) | 13 | Cheez-It Bowl - Orlando FL | vs B12 |
| vs Clemson | vs Other Opponents | Clemson compared to OOs | |
| Record: | 3-10 | 89-64 | |
| Points Scored: | 14.85 | 31.04 | 16.19 |
| Points Allowed: | 26.31 | 24.80 | 1.51 |
| Margin: | -11.46 | 6.24 | 17.70 |
| Total Points: | 41.16 | 55.84 | -14.68 |