| 9/4/2021 | Eastern Illinois (1-10) | 0 | at | South Carolina | 46 | OVC (1AA) | ||
| 9/11/2021 | South Carolina | 20 | at | East Carolina (7-5) | 17 | at AAC | ||
| 9/18/2021 | South Carolina | 13 | at | Georgia (14-1,9-1) | 40 | |||
| 9/25/2021 | Kentucky (10-3,5-3) | 16 | at | South Carolina | 10 | |||
| 10/2/2021 | Troy (5-7) | 14 | at | South Carolina | 23 | SBC | ||
| 10/9/2021 | South Carolina | 20 | at | Tennessee (7-6,4-4) | 45 | |||
| 10/16/2021 | Vanderbilt (2-10,0-8) | 20 | at | South Carolina | 21 | |||
| 10/23/2021 | South Carolina | 14 | at | Texas A&M (8-4,4-4) | 44 | |||
| 11/6/2021 | Florida (6-7,2-6) | 17 | at | South Carolina | 40 | |||
| 11/13/2021 | South Carolina | 28 | at | Missouri (6-7,3-5) | 31 | |||
| 11/20/2021 | Auburn (6-7,3-5) | 17 | at | South Carolina | 21 | |||
| 11/27/2021 | Clemson (10-3) | 30 | at | South Carolina | 0 | ACC | ||
| 12/30/2021 | North Carolina (6-7) | 21 | vs | South Carolina | 38 | Dukes Mayo Bowl - Charlotte NC | ACC |
| vs South Carolina | vs Other Opponents | South Carolina compared to OOs | |
| Record: | 6-7 | 82-70 | |
| Points Scored: | 24.00 | 29.43 | 5.43 |
| Points Allowed: | 22.62 | 24.74 | -2.12 |
| Margin: | 1.38 | 4.69 | 3.31 |
| Total Points: | 46.62 | 54.17 | -7.55 |