Estadio: Bridgeforth Stadium and Zane Showker Field Round: 1
Home Manager: Curt Cignetti Away Manager: Frank Scelfo
| NCAAF | 2021/11/28 00:00 | Florida A&M v SE Louisiana Lions | W | 14-38 |
| NCAAF | 2021/11/19 00:00 | Nicholls Colonels v SE Louisiana Lions | L | 45-42 |
| NCAAF | 2021/11/14 00:00 | Northwestern State v SE Louisiana Lions | W | 28-56 |
| NCAAF | 2021/11/06 19:00 | SE Louisiana Lions v Incarnate Word | L | 52-55 |
| NCAAF | 2021/10/30 23:00 | McNeese State Cowboys v SE Louisiana Lions | W | 20-23 |
| NCAAF | 2021/10/23 20:00 | SE Louisiana Lions v Northwestern State | W | 51-14 |
| NCAAF | 2021/10/16 21:00 | Houston Christian v SE Louisiana Lions | W | 24-61 |
| NCAAF | 2021/10/09 17:00 | SE Louisiana Lions v Nicholls Colonels | W | 58-48 |
| NCAAF | 2021/11/20 19:00 | Towson v James Madison | W | 10-56 |
| NCAAF | 2021/11/13 20:30 | James Madison v William & Mary | W | 32-22 |
| NCAAF | 2021/11/06 19:30 | Campbell v James Madison | W | 14-51 |
| NCAAF | 2021/10/30 18:00 | Elon v James Madison | W | 21-45 |
| NCAAF | 2021/10/23 19:00 | James Madison v Delaware | W | 22-10 |
| NCAAF | 2021/10/16 18:00 | James Madison v Richmond Spiders | W | 19-3 |
| NCAAF | 2021/10/09 18:00 | Villanova Wildcats v James Madison | L | 28-27 |
| NCAAF | 2021/10/02 19:30 | James Madison v New Hampshire | W | 23-21 |