| 9/2/2021 | Tennessee-Martin (10-3) | 21 | at | Western Kentucky | 59 | OVC (1AA) | ||
| 9/11/2021 | Western Kentucky | 35 | at | Army (9-4) | 38 | at Ind | ||
| 9/25/2021 | Indiana (2-10) | 33 | at | Western Kentucky | 31 | B10 | ||
| 10/2/2021 | Western Kentucky | 31 | at | Michigan State (11-2) | 48 | at B10 | ||
| 10/9/2021 | Texas-San Antonio (12-2,8-1) | 52 | at | Western Kentucky | 46 | |||
| 10/16/2021 | Western Kentucky | 43 | at | Old Dominion (6-7,5-3) | 20 | |||
| 10/23/2021 | Western Kentucky | 34 | at | Florida Intl (1-11,0-8) | 19 | |||
| 10/30/2021 | UNC-Charlotte (5-7,3-5) | 13 | at | Western Kentucky | 45 | |||
| 11/6/2021 | Middle Tenn State (7-6,4-4) | 21 | at | Western Kentucky | 48 | |||
| 11/13/2021 | Western Kentucky | 42 | at | Rice (4-8,3-5) | 21 | |||
| 11/20/2021 | Florida Atlantic (5-7,3-5) | 17 | at | Western Kentucky | 52 | |||
| 11/27/2021 | Western Kentucky | 53 | at | Marshall (7-6,5-3) | 21 | |||
| 12/3/2021 | Western Kentucky | 41 | at | Texas-San Antonio (12-2,8-1) | 49 | CUSA Championship | ||
| 12/18/2021 | Western Kentucky | 59 | vs | Appalachian State (10-4) | 38 | Boca Raton Bowl - Boca Raton | vs SBC |
| vs Western Kentucky | vs Other Opponents | Western Kentucky compared to OOs | |
| Record: | 5-9 | 94-70 | |
| Points Scored: | 29.36 | 29.58 | 0.22 |
| Points Allowed: | 44.21 | 26.55 | 17.66 |
| Margin: | -14.85 | 3.03 | 17.88 |
| Total Points: | 73.57 | 56.13 | 17.44 |