Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | South Carolina State | 41 | Alabama A&M | 42 | Final | L | -1 |
| 2 | 2021-09-11 | South Carolina State | 3 | Clemson | 49 | Final | L | -46 |
| 3 | 2021-09-18 | South Carolina State | 35 | New Mexico State | 43 | Final | L | -8 |
| 4 | 2021-10-02 | Bethune-Cookman | 35 | South Carolina State | 42 | Final | W | 7 |
| 5 | 2021-10-09 | South Carolina State | 7 | Florida A&M | 30 | Final | L | -23 |
| 6 | 2021-10-16 | Morgan State | 14 | South Carolina State | 37 | Final | W | 23 |
| 7 | 2021-10-23 | South Carolina State | 13 | Delaware State | 7 | Final | W | 6 |
| 8 | 2021-10-30 | South Carolina State | 27 | North Carolina Central | 24 | Final | W | 3 |
| 9 | 2021-11-06 | Howard | 12 | South Carolina State | 15 | Final | W | 3 |
| 10 | 2021-11-13 | North Carolina A&T | 27 | South Carolina State | 17 | Final | L | -10 |
| 11 | 2021-11-20 | South Carolina State | 31 | Norfolk State | 21 | Final | W | 10 |
| 12 | 2021-12-18 | South Carolina State (187) | 31 | Jackson State (110) | 10 | Final | W | 21 |