Stadium: Cajun Field Round: 1
Home Manager: Michael Desormeaux Away Manager: Frank Scelfo
| NCAAF | 2021/12/04 19:00 | SE Louisiana v James Madison | L | 20-59 |
| NCAAF | 2021/11/28 00:00 | Florida A&M v SE Louisiana | W | 14-38 |
| NCAAF | 2021/11/19 00:00 | Nicholls State v SE Louisiana | L | 45-42 |
| NCAAF | 2021/11/14 00:00 | Northwestern State v SE Louisiana | W | 28-56 |
| NCAAF | 2021/11/06 19:00 | SE Louisiana v Incarnate Word | L | 52-55 |
| NCAAF | 2021/10/30 23:00 | McNeese State v SE Louisiana | W | 20-23 |
| NCAAF | 2021/10/23 20:00 | SE Louisiana v Northwestern State | W | 51-14 |
| NCAAF | 2021/10/16 21:00 | Houston Christian v SE Louisiana | W | 24-61 |
| NCAAF | 2022/09/03 16:30 | Sacred Heart v Lafayette | W | 0-6 |
| NCAAF Bowl Games | 2021/12/19 02:15 | Marshall v Lafayette | W | 21-36 |
| NCAAF | 2021/12/04 20:30 | Appalachian St v Lafayette | W | 16-24 |
| NCAAF | 2021/11/27 21:00 | UL Monroe v Lafayette | W | 16-21 |
| NCAAF | 2021/11/20 21:00 | Lafayette v Libertay | W | 42-14 |
| NCAAF | 2021/11/20 17:00 | Lafayette v Lehigh | L | 10-17 |
| NCAAF | 2021/11/13 20:30 | Lafayette v Troy | W | 35-21 |
| NCAAF | 2021/11/13 17:30 | Colgate v Lafayette | L | 20-13 |