| 9/3/2021 | South Dakota | 14 | at | Kansas (2-10) | 17 | at B12 | ||
| 9/11/2021 | Northern Arizona (5-6) | 7 | at | South Dakota | 34 | BSky | ||
| 9/18/2021 | South Dakota | 48 | at | Cal Poly (2-9) | 14 | at BSky | ||
| 9/25/2021 | South Dakota | 23 | at | Missouri State (8-4,6-2) | 31 | |||
| 10/2/2021 | Indiana State (5-6,3-5) | 10 | at | South Dakota | 38 | |||
| 10/9/2021 | North Dakota (5-6,3-5) | 13 | at | South Dakota | 20 | |||
| 10/16/2021 | South Dakota | 34 | at | Northern Iowa (6-6,4-4) | 21 | |||
| 10/23/2021 | Illinois State (4-7,2-6) | 20 | at | South Dakota | 14 | |||
| 11/6/2021 | South Dakota | 42 | at | Western Illinois (2-9,2-6) | 21 | |||
| 11/13/2021 | South Dakota State (11-4,5-3) | 20 | at | South Dakota | 23 | |||
| 11/20/2021 | South Dakota | 24 | at | North Dakota State (14-1,8-1) | 52 | |||
| 11/27/2021 | Southern Illinois (8-5,6-4) | 22 | at | South Dakota | 10 |
| vs South Dakota | vs Other Opponents | South Dakota compared to OOs | |
| Record: | 5-7 | 67-66 | |
| Points Scored: | 20.67 | 26.47 | 5.80 |
| Points Allowed: | 27.00 | 26.30 | 0.70 |
| Margin: | -6.33 | 0.17 | 6.50 |
| Total Points: | 47.67 | 52.77 | -5.10 |