Stadium: William B. Greene Jr. Stadium Round: 1
Home Manager: George Quarles Away Manager:
| NCAAF | 2021/12/11 17:00 | East Tennessee State v North Dakota State | L | 3-27 |
| NCAAF | 2021/12/04 19:00 | Kennesaw State v East Tennessee State | W | 31-32 |
| NCAAF | 2021/11/20 18:00 | Mercer v East Tennessee State | W | 35-38 |
| NCAAF | 2021/11/13 19:00 | East Tennessee State v Western Carolina | W | 56-35 |
| NCAAF | 2021/11/06 17:00 | VMI v East Tennessee State | W | 20-27 |
| NCAAF | 2021/10/23 18:00 | East Tennessee State v Furman | W | 17-13 |
| NCAAF | 2021/10/16 17:30 | East Tennessee State v Tennessee Chattanooga | L | 16-21 |
| NCAAF | 2021/10/09 20:30 | The Citadel v East Tennessee State | W | 21-48 |
| NCAAF | 2021/11/13 20:00 | Wingate Bulldogs v Mars Hill Lions | L | 26-19 |
| NCAAF | 2021/11/06 17:00 | Mars Hill Lions v Tusculum Pioneers | W | 20-7 |
| NCAAF | 2021/10/30 19:00 | Carson–Newman Eagles v Mars Hill Lions | W | 23-49 |
| NCAAF | 2021/10/23 17:00 | Mars Hill Lions v Catawba College | W | 31-14 |
| NCAAF | 2021/10/16 20:00 | Limestone Saints v Mars Hill Lions | W | 3-32 |
| NCAAF | 2021/10/09 17:30 | Mars Hill Lions v Barton Bulldogs | W | 40-32 |
| NCAAF | 2021/10/02 17:00 | Mars Hill Lions v Newberry Wolves | W | 28-22 |
| NCAAF | 2021/09/25 22:00 | Lenoir Rhyne Bears v Mars Hill Lions | L | 31-16 |