| 2021-09-23 19:00:4309/23/2021 | East Lawrence vs Hatton | 14 - 30 | Eagle Stadium |
| 2021-09-24 19:00:0009/24/2021 | Hartselle vs Russellville | 58 - 21 | J.P. Cain Stadium |
| 2021-09-24 19:00:0009/24/2021 | Cullman vs Mars Hill | 49 - 7 | Cullman High School |
| 2021-09-24 19:00:0009/24/2021 | West Morgan vs Leeds | 13 - 37 | Rebels Stadium |
| 2021-09-24 19:00:0009/24/2021 | Priceville vs Danville | 35 - 12 | Bulldog Stadium |
| 2021-09-24 19:00:0009/24/2021 | Lee vs James Clemens | 55 - 15 | Milton Frank Stadium |
| 2021-09-24 19:00:0009/24/2021 | Bob Jones vs Auburn | 42 - 21 | Auburn High School |
| 2021-09-24 19:00:0009/24/2021 | Mae Jemison vs Buckhorn | 24 - 48 | Louis Crews Stadium |
| 2021-09-24 19:00:0009/24/2021 | Rogers vs Lauderdale Co. | 8 - 33 | Pirate Field |
| 2021-09-24 19:00:0009/24/2021 | Phil Campbell vs Haleyville | 12 - 13 | Phil Campbell High School |
| 2021-09-24 19:00:0109/24/2021 | Elkmont vs Lexington | 0 - 48 | Boss Hill Stadium |
| 2021-09-24 19:00:0309/24/2021 | Sheffield vs Central | 13 - 47 | |
| 2021-09-24 19:00:0309/24/2021 | Cedar Bluff vs North Sand Mtn | 6 - 22 | Cedar Bluff High School |
| 2021-09-24 19:00:0409/24/2021 | West Limestone vs East Limestone | 31 - 28 | West Limestone High School |
| 2021-09-24 19:00:1009/24/2021 | Albertville vs Boaz | 21 - 35 | Albertville High School |
| 2021-09-24 19:00:1809/24/2021 | Tharptown vs Cherokee | 64 - 0 | |
| 2021-09-24 19:00:2009/24/2021 | Vina vs Lynn | 0 - 49 | |
| 2021-09-24 19:00:2109/24/2021 | Colbert Heights vs Colbert Co. | 0 - 25 | Amos Mitchell Stadium |
| 2021-09-24 19:00:2709/24/2021 | Tanner vs Columbia | 41 - 8 | Rip Swanner Stadium |
| 2021-09-24 19:00:2709/24/2021 | Ider vs Valley Head | 42 - 20 | Wayne C. Hardiman Stadium |
| 2021-09-24 19:00:2909/24/2021 | Arab vs Brewer | 49 - 13 | Arab High School |
| 2021-09-24 19:00:3409/24/2021 | Hubbertville vs Hackleburg | 51 - 24 | |
| 2021-09-24 19:00:3609/24/2021 | Falkville vs Cold Springs | 49 - 7 | Burl Vest Stadium |
| 2021-09-24 19:00:3909/24/2021 | Hueytown vs Athens | 54 - 20 | |
| 2021-09-24 19:00:4009/24/2021 | Ardmore vs Clements | 55 - 27 | Ardmore High School |
| 2021-09-24 19:00:4409/24/2021 | Whitesburg Christian vs Shoals Christian | 61 - 14 | |
| 2021-09-24 19:00:4809/24/2021 | Pisgah vs DAR | 58 - 28 | Sam Kenimer Stadium |
| 2021-09-24 19:00:5009/24/2021 | Marion Co. vs Phillips | 40 - 12 | |
| 2021-09-24 19:00:5509/24/2021 | Woodville vs Decatur Heritage | 14 - 55 | Woodville High School |
| 2021-09-24 19:00:5709/24/2021 | Lawrence Co. vs Westminster Christian | 20 - 23 | Lawerence County High School |
