| 9/4/2021 | Monmouth NJ (7-4) | 15 | at | Middle Tenn State | 50 | BigS (1AA) | ||
| 9/11/2021 | Middle Tenn State | 14 | at | Virginia Tech (6-7) | 35 | at ACC | ||
| 9/18/2021 | Middle Tenn State | 13 | at | Texas-San Antonio (12-2,8-1) | 27 | |||
| 9/24/2021 | Middle Tenn State | 39 | at | UNC-Charlotte (5-7,3-5) | 42 | |||
| 10/2/2021 | Marshall (7-6,5-3) | 28 | at | Middle Tenn State | 34 | |||
| 10/9/2021 | Middle Tenn State | 13 | at | Liberty (8-5) | 41 | at Ind | ||
| 10/22/2021 | Middle Tenn State | 44 | at | Connecticut (1-11) | 13 | at Ind | ||
| 10/30/2021 | Southern Miss (3-9,2-6) | 10 | at | Middle Tenn State | 35 | |||
| 11/6/2021 | Middle Tenn State | 21 | at | Western Kentucky (9-5,7-2) | 48 | |||
| 11/13/2021 | Florida Intl (1-11,0-8) | 10 | at | Middle Tenn State | 50 | |||
| 11/20/2021 | Old Dominion (6-7,5-3) | 24 | at | Middle Tenn State | 17 | |||
| 11/27/2021 | Middle Tenn State | 27 | at | Florida Atlantic (5-7,3-5) | 17 | |||
| 12/17/2021 | Middle Tenn State | 31 | vs | Toledo (7-6) | 24 | Bahamas Bowl - Nassau | vs MAC |
| vs Middle Tenn State | vs Other Opponents | Middle Tenn State compared to OOs | |
| Record: | 6-7 | 71-80 | |
| Points Scored: | 25.69 | 29.11 | 3.42 |
| Points Allowed: | 29.85 | 27.96 | 1.89 |
| Margin: | -4.16 | 1.15 | 5.31 |
| Total Points: | 55.54 | 57.07 | -1.53 |