| 9/2/2021 | Mississippi Valley State | 0 | at | Murray State (6-5) | 35 | at OVC | ||
| 9/18/2021 | Mississippi Valley State | 13 | at | Stephen F. Austin (8-4) | 58 | at WAC | ||
| 9/26/2021 | Southern (4-7,3-5) | 38 | vs | Mississippi Valley State | 25 | Jackson MS | ||
| 10/2/2021 | North Carolina Central (6-5) | 16 | at | Mississippi Valley State | 17 | MEAC | ||
| 10/9/2021 | Mississippi Valley State | 20 | at | Bethune-Cookman (2-9,2-6) | 14 | |||
| 10/16/2021 | Alcorn State (6-5,5-3) | 24 | at | Mississippi Valley State | 12 | |||
| 10/23/2021 | Florida A&M (9-3,7-1) | 31 | at | Mississippi Valley State | 28 | |||
| 10/30/2021 | Jackson State (11-2,9-0) | 28 | at | Mississippi Valley State | 19 | |||
| 11/6/2021 | Mississippi Valley State | 14 | at | Alabama A&M (7-3,5-3) | 42 | |||
| 11/13/2021 | Alabama State (5-6,3-5) | 31 | at | Mississippi Valley State | 44 | |||
| 11/27/2021 | Mississippi Valley State | 24 | at | Prairie View (7-5,6-3) | 19 |
| vs Mississippi Valley State | vs Other Opponents | Mississippi Valley State compared to OOs | |
| Record: | 7-4 | 64-50 | |
| Points Scored: | 30.55 | 26.68 | -3.87 |
| Points Allowed: | 19.64 | 26.11 | -6.47 |
| Margin: | 10.91 | 0.57 | -10.34 |
| Total Points: | 50.19 | 52.79 | -2.60 |