| 9/2/2021 | South Florida | 0 | at | North Carolina State (9-3) | 45 | at ACC | ||
| 9/11/2021 | Florida (6-7) | 42 | at | South Florida | 20 | SEC | ||
| 9/18/2021 | Florida A&M (9-3) | 17 | at | South Florida | 38 | SWAC (1AA) | ||
| 9/25/2021 | South Florida | 27 | at | BYU (10-3) | 35 | at Ind | ||
| 10/2/2021 | South Florida | 17 | at | SMU (8-4,4-4) | 41 | |||
| 10/16/2021 | Tulsa (7-6,5-3) | 32 | at | South Florida | 31 | |||
| 10/23/2021 | Temple (3-9,1-7) | 14 | at | South Florida | 34 | |||
| 10/28/2021 | South Florida | 14 | at | East Carolina (7-5,5-3) | 29 | |||
| 11/6/2021 | Houston (12-2,8-1) | 54 | at | South Florida | 42 | |||
| 11/12/2021 | Cincinnati (13-1,9-0) | 45 | at | South Florida | 28 | |||
| 11/20/2021 | South Florida | 14 | at | Tulane (2-10,1-7) | 45 | |||
| 11/26/2021 | South Florida | 13 | at | UCF (9-4,5-3) | 17 |
| vs South Florida | vs Other Opponents | South Florida compared to OOs | |
| Record: | 10-2 | 85-55 | |
| Points Scored: | 34.67 | 30.45 | -4.22 |
| Points Allowed: | 23.17 | 25.24 | -2.07 |
| Margin: | 11.50 | 5.21 | -6.29 |
| Total Points: | 57.84 | 55.69 | 2.15 |