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