| 9/4/2021 | Midwestern State | 48 | at | Quincy (4-7) | 27 | at GLV | ||
| 9/11/2021 | Midwestern State | 31 | vs | Texas A&M-Commerce (7-4,5-2) | 30 | Arlington TX | ||
| 9/18/2021 | Midwestern State | 35 | at | Angelo State (11-3,5-2) | 17 | |||
| 9/25/2021 | Eastern New Mexico (4-7,1-6) | 24 | at | Midwestern State | 31 | OT | ||
| 10/2/2021 | Midwestern State | 20 | at | Central Washington (8-3) | 30 | at GNWAC | ||
| 10/9/2021 | Texas A&M-Kingsville (5-5,3-4) | 13 | at | Midwestern State | 30 | |||
| 10/23/2021 | Midwestern State | 14 | at | Tarleton State (6-5) | 17 | at WAC | ||
| 10/30/2021 | Western New Mexico (1-9,0-7) | 10 | at | Midwestern State | 52 | |||
| 11/6/2021 | Midwestern State | 12 | at | West Texas A&M (7-4,5-2) | 15 | |||
| 11/13/2021 | Texas-Permian Basin (5-6,3-4) | 30 | at | Midwestern State | 36 |
| vs Midwestern State | vs Other Opponents | Midwestern State compared to OOs | |
| Record: | 3-7 | 55-46 | |
| Points Scored: | 21.30 | 32.09 | 10.79 |
| Points Allowed: | 30.90 | 25.76 | 5.14 |
| Margin: | -9.60 | 6.33 | 15.93 |
| Total Points: | 52.20 | 57.85 | -5.65 |