| 8/28/2021 | Eastern Illinois | 21 | at | Indiana State | 26 | @ MVC | ||
| 9/2/2021 | Austin Peay | 30 | at | Chattanooga | 20 | @ SoCon | ||
| Mississippi Valley State | 0 | at | Murray State | 35 | SWAC | |||
| Tennessee Tech | 14 | at | Samford | 52 | @ SoCon | |||
| Southern Illinois | 47 | at | SE Missouri State | 21 | MVC | |||
| Tennessee-Martin | 21 | at | Western Kentucky | 59 | @ CUSA (1A) | |||
| 9/4/2021 | Eastern Illinois | 0 | at | South Carolina | 46 | @ SEC (1A) | ||
| 9/5/2021 | Tennessee State | 10 | vs | Grambling | 16 | Canton OH | vs SWAC | |
| 9/11/2021 | Murray State | 7 | at | Cincinnati | 42 | @ AAC (1A) | ||
| Eastern Illinois | 10 | at | Dayton | 17 | @ Pio | |||
| Tennessee State | 16 | vs | Jackson State | 38 | Memphis TN | vs SWAC | ||
| Austin Peay | 17 | at | Mississippi | 54 | @ SEC (1A) | |||
| SE Missouri State | 14 | at | Sam Houston | 52 | @ WAC | |||
| Furman | 26 | at | Tennessee Tech | 0 | SoCon | |||
| Samford | 27 | at | Tennessee-Martin | 33 | SoCon | |||
| 9/18/2021 | Morehead State | 35 | at | Austin Peay | 59 | Pio | ||
| Murray State | 10 | at | Bowling Green | 27 | @ MAC (1A) | |||
| Illinois State | 31 | at | Eastern Illinois | 24 | MVC | |||
| SE Missouri State | 28 | at | Missouri | 59 | @ SEC (1A) | |||
| Tennessee-Martin | 35 | at | Northwestern State | 10 | @ SLC | |||
| Tennessee Tech | 0 | at | Tennessee | 56 | @ SEC (1A) | |||
| Kentucky State | 7 | at | Tennessee State | 41 | SIAC (D2) | |||
| 9/25/2021 | Austin Peay | 27 | at | Eastern Kentucky | 35 | @ WAC | ||
| Tennessee-Martin | 34 | at | Jacksonville State | 31 | @ WAC | |||
| Tennessee State | 14 | at | SE Missouri State | 47 | ||||
| Eastern Illinois | 28 | at | Tennessee Tech | 14 | ||||
| 10/2/2021 | Tennessee State | 24 | at | Austin Peay | 22 | |||
| Eastern Illinois | 6 | at | Murray State | 22 | ||||
| SE Missouri State | 17 | at | Tennessee Tech | 28 | ||||
| 10/9/2021 | SE Missouri State | 30 | at | Austin Peay | 14 | |||
| Tennessee Tech | 27 | at | North Carolina Central | 16 | @ MEAC | |||
| Murray State | 24 | at | Tennessee-Martin | 48 | ||||
| 10/16/2021 | Tennessee-Martin | 28 | at | Eastern Illinois | 17 | |||
| Murray State | 32 | at | SE Missouri State | 31 | ||||
| Tennessee Tech | 13 | at | Tennessee State | 20 | ||||
| 10/23/2021 | Tennessee State | 28 | at | Eastern Illinois | 0 | |||
| Austin Peay | 47 | at | Murray State | 6 | ||||
| Virginia U-Lynchburg | 13 | at | Tennessee Tech | 56 | None (Unk?) | |||
| SE Missouri State | 30 | at | Tennessee-Martin | 38 | ||||
| 10/30/2021 | Eastern Illinois | 15 | at | SE Missouri State | 38 | |||
| Murray State | 21 | at | Tennessee State | 27 | ||||
| Austin Peay | 16 | at | Tennessee-Martin | 17 | ||||
| 11/6/2021 | Eastern Illinois | 26 | at | Austin Peay | 42 | |||
| Tennessee Tech | 27 | at | Murray State | 32 | ||||
| Tennessee State | 20 | at | Tennessee-Martin | 41 | ||||
| 11/13/2021 | SE Missouri State | 10 | at | Murray State | 28 | |||
| Austin Peay | 36 | at | Tennessee State | 7 | ||||
| Tennessee-Martin | 42 | at | Tennessee Tech | 3 | ||||
| 11/20/2021 | Tennessee Tech | 20 | at | Austin Peay | 48 | |||
| Murray State | 20 | at | Eastern Illinois | 13 | ||||
| Tennessee State | 10 | at | Mississippi State | 55 | @ SEC (1A) | |||
| Tennessee-Martin | 14 | at | SE Missouri State | 31 | ||||
| 11/27/2021 | Tennessee-Martin | 32 | at | Missouri State | 31 | @ MVC | ||
| 12/4/2021 | Tennessee-Martin | 7 | at | Montana State | 26 | @ BSky |