| Date | H/A | W/L | Team | Score | Opponent | Score | ||
| 2021-08-27 | A | W | Madonna | 58 | Beallsville (OH) () | 14 | 412 | |
| 2021-09-04 | A | W | Madonna | 1 | Carrick (PA) () | 0 | 413 | |
| 2021-09-11 | A | W | Madonna | 41 | Bridgeport (OH) () | 20 | 414 | |
| 2021-09-17 | H | W | Madonna | 14 | Mathews (OH) () | 6 | 415 | |
| 2021-09-28 | H | L | Madonna | 20 | Cameron () | 38 | 482 | |
| 2021-10-08 | A | L | Madonna | 16 | Toronto (OH) () | 19 | 416 | |
| 2021-10-15 | H | W | Madonna | 28 | Steubenville Central (OH) () | 7 | 417 | |
| 2021-10-23 | H | L | Madonna | 28 | Conotton Valley (OH) () | 40 | 418 | |
| 2021-10-29 | A | W | Madonna | 58 | Hundred () | 0 | 534 | |
| 2021-11-05 | A | L | Madonna | 14 | Trinity () | 31 | 540 |