| 9/4/2021 | Southern Miss | 7 | at | South Alabama (5-7) | 31 | at SBC | ||
| 9/11/2021 | Grambling (4-7) | 0 | at | Southern Miss | 37 | SWAC (1AA) | ||
| 9/18/2021 | Troy (5-7) | 21 | at | Southern Miss | 9 | SBC | ||
| 9/25/2021 | Southern Miss | 14 | at | Alabama (13-2) | 63 | at SEC | ||
| 10/2/2021 | Southern Miss | 19 | at | Rice (4-8,3-5) | 24 | |||
| 10/9/2021 | UTEP (7-6,4-4) | 26 | at | Southern Miss | 13 | |||
| 10/16/2021 | UAB (9-4,6-2) | 34 | at | Southern Miss | 0 | |||
| 10/30/2021 | Southern Miss | 10 | at | Middle Tenn State (7-6,4-4) | 35 | |||
| 11/6/2021 | North Texas (6-7,5-3) | 38 | at | Southern Miss | 14 | |||
| 11/13/2021 | Southern Miss | 17 | at | Texas-San Antonio (12-2,8-1) | 27 | |||
| 11/19/2021 | Southern Miss | 35 | at | Louisiana Tech (3-9,2-6) | 19 | |||
| 11/27/2021 | Florida Intl (1-11,0-8) | 17 | at | Southern Miss | 37 |
| vs Southern Miss | vs Other Opponents | Southern Miss compared to OOs | |
| Record: | 9-3 | 67-73 | |
| Points Scored: | 27.92 | 27.39 | -0.53 |
| Points Allowed: | 17.67 | 28.63 | -10.96 |
| Margin: | 10.25 | -1.24 | -11.49 |
| Total Points: | 45.59 | 56.02 | -10.43 |