| Date |
|
Score |
|
Score |
|
|
| 2021-08-19 | Bellaire (OH) | 34 | River (OH) ** | 14 | | |
| 2021-08-20 | Pineville (KY) | 26 | Phelps (KY) ** | 20 | | |
| 2021-08-20 | Raceland (KY) | 16 | Ashland (KY) ** | 7 | | |
| 2021-08-20 | Cambridge (OH) ** | 27 | Indian Creek (OH) | 7 | | |
| 2021-08-20 | Cincinnati Country Day (OH) ** | 56 | Manchester (OH) | 0 | | |
| 2021-08-20 | Conotton Valley (OH) ** | 48 | Strasburg-Franklin (OH) | 8 | | |
| 2021-08-20 | Frontier (OH) ** | 34 | Bridgeport (OH) | 20 | | |
| 2021-08-20 | Gallia Academy (OH) ** | 22 | Meigs (OH) | 19 | | |
| 2021-08-20 | Indian Valley (OH) | 37 | Beaver Local (OH) ** | 26 | | |
| 2021-08-20 | Mathews (OH) ** | 6 | Steubenville Central (OH) | 0 | | |
| 2021-08-20 | Miami Valley Christian (OH) ** | 38 | Millersport (OH) | 6 | | |
| 2021-08-20 | Miller (OH) ** | 36 | Beallsville (OH) | 16 | | |
| 2021-08-20 | New Philadelphia (OH) | 48 | Marietta (OH) ** | 7 | | |
| 2021-08-20 | Perry (OH) ** | 26 | Painesville Riverside (OH) | 6 | | |
| 2021-08-20 | Racine Southern (OH) ** | 37 | Federal Hocking (OH) | 8 | | |
| 2021-08-20 | Reedsville Eastern (OH) ** | 39 | Green (OH) | 8 | | |
| 2021-08-20 | Shadyside (OH) ** | 26 | Martins Ferry (OH) | 6 | | |
| 2021-08-20 | St. Clairsville (OH) | 42 | Carrollton (OH) ** | 35 | | |
| 2021-08-20 | Steubenville (OH) ** | 22 | Olentangy Liberty (OH) | 7 | | |
| 2021-08-20 | Symmes Valley (OH) | 42 | South Gallia (OH) ** | 0 | | |
| 2021-08-20 | Toronto (OH) ** | 33 | Pepper Pike Orange (OH) | 20 | | |
| 2021-08-20 | Union Local (OH) | 40 | Monroe Central (OH) ** | 18 | | |
| 2021-08-20 | Villa Angela St. Joe (OH) ** | 44 | Cuyahoga Valley CA (OH) | 12 | | |
| 2021-08-20 | Warren Local (OH) ** | 47 | Belpre (OH) | 12 | | |
| 2021-08-20 | Waterford (OH) | 29 | Crooksville (OH) ** | 7 | | |
| 2021-08-20 | West Branch (OH) | 46 | East Liverpool (OH) ** | 6 | | |
| 2021-08-20 | West Muskingum (OH) ** | 32 | John Glenn (OH) | 0 | | |
| 2021-08-21 | Fairland (OH) | 28 | Portsmouth West (OH) ** | 27 | | |
| 2021-08-21 | Trimble (OH) ** | 7 | Nelsonville-York (OH) | 6 | | |
| 2021-08-21 | Tuscarawas Cent. Cath. (OH) ** | 31 | Fisher Catholic (OH) | 17 | | |
| 2021-08-21 | Christiansburg (VA) | 57 | Giles (VA) ** | 0 | | |