| Date | H/A | W/L | Team | Score | Opponent | Score | ||
| 2021-08-27 | A | W | Madonna | 58 | Beallsville (OH) (2) | 14 | Hx 412 | |
| 2021-09-04 | A | W | Madonna | 1 | Carrick (PA) (0) | 0 | Hx 413 | |
| 2021-09-11 | A | W | Madonna | 41 | Bridgeport (OH) (3) | 20 | Hx 414 | |
| 2021-09-17 | H | W | Madonna | 14 | Mathews (OH) (6) | 6 | Hx 415 | |
| 2021-09-28 | H | L | Madonna | 20 | Cameron (9) | 38 | Hx 482 | |
| 2021-10-08 | A | L | Madonna | 16 | Toronto (OH) (5) | 19 | Hx 416 | |
| 2021-10-15 | H | W | Madonna | 28 | Steubenville Central (OH) (3) | 7 | Hx 417 | |
| 2021-10-23 | H | L | Madonna | 28 | Conotton Valley (OH) (5) | 40 | Hx 418 | |
| 2021-10-29 | A | W | Madonna | 58 | Hundred (0) | 0 | Hx 534 | |
| 2021-11-05 | A | L | Madonna | 14 | Trinity (7) | 31 | Hx 540 |