Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Eastern Illinois | 0 | South Carolina | 46 | Final | W | 46 |
| 2 | 2021-09-11 | South Carolina | 20 | East Carolina | 17 | Final | W | 3 |
| 3 | 2021-09-18 | South Carolina | 13 | Georgia | 40 | Final | L | -27 |
| 4 | 2021-09-25 | Kentucky | 16 | South Carolina | 10 | Final | L | -6 |
| 5 | 2021-10-02 | Troy | 14 | South Carolina | 23 | Final | W | 9 |
| 6 | 2021-10-09 | South Carolina | 20 | Tennessee | 45 | Final | L | -25 |
| 7 | 2021-10-16 | Vanderbilt | 20 | South Carolina | 21 | Final | W | 1 |
| 8 | 2021-10-23 | South Carolina | 14 | Texas A&M | 44 | Final | L | -30 |
| 9 | 2021-11-06 | Florida | 17 | South Carolina | 40 | Final | W | 23 |
| 10 | 2021-11-13 | South Carolina | 28 | Missouri | 31 | Final | L | -3 |
| 11 | 2021-11-20 | Auburn | 17 | South Carolina | 21 | Final | W | 4 |
| 12 | 2021-11-27 | Clemson (17) | 30 | South Carolina (64) | 0 | Final | L | -30 |
| 13 | 2021-12-30 | North Carolina (63) | 21 | South Carolina (56) | 38 | Final | W | 17 |