| 8/28/2021 | Eastern Illinois (1-10) | 21 | at | Indiana State | 26 | OVC | ||
| 9/11/2021 | Indiana State | 6 | at | Northwestern (3-9) | 24 | at B10 | ||
| 9/18/2021 | Indiana State | 23 | at | Eastern Kentucky (7-4) | 21 | at WAC | ||
| 9/25/2021 | South Dakota State (11-4,5-3) | 44 | at | Indiana State | 0 | |||
| 10/2/2021 | Indiana State | 10 | at | South Dakota (7-5,5-4) | 38 | |||
| 10/9/2021 | Western Illinois (2-9,2-6) | 27 | at | Indiana State | 37 | |||
| 10/16/2021 | Indiana State | 7 | at | Missouri State (8-4,6-2) | 37 | |||
| 10/23/2021 | Youngstown State (3-7,2-6) | 17 | at | Indiana State | 28 | |||
| 10/30/2021 | Indiana State | 2 | at | North Dakota State (14-1,8-1) | 44 | |||
| 11/13/2021 | Southern Illinois (8-5,6-4) | 47 | at | Indiana State | 21 | |||
| 11/20/2021 | Indiana State | 15 | at | Illinois State (4-7,2-6) | 10 |
| vs Indiana State | vs Other Opponents | Indiana State compared to OOs | |
| Record: | 6-5 | 62-60 | |
| Points Scored: | 30.00 | 26.56 | -3.44 |
| Points Allowed: | 15.91 | 25.80 | -9.89 |
| Margin: | 14.09 | 0.76 | -13.33 |
| Total Points: | 45.91 | 52.36 | -6.45 |