| Sat 31/07/21 | Maine Road v FC Isle of Man | 1-1 | | | | | |
| Mon 02/08/21 | Maine Road v Wythenshawe Amateurs * | 2-3 | | | | | |
| Sat 07/08/21 | Alsager Town v Maine Road | 3-1 |  | |  | |  |
| Sat 14/08/21 | Maine Road v Rocester | 3-1 | | | | | |
| Tue 17/08/21 | Abbey Hey v Maine Road | 4-0 | | | | | |
| Sat 21/08/21 | Maine Road v Sandbach United | 1-2 | | | | | |
| Mon 30/08/21 | West Didsbury & Chorlton v Maine Road | 3-2 | | | | | |
| Sat 04/09/21 | Abbey Hulton United v Maine Road | 3-2 | | | | | |
| Sun 12/09/21 | Worsbrough Bridge Athletic v Maine Road | 1-2 | | | | | |
| Sat 18/09/21 | Maine Road v Ellesmere Rangers | 3-2 | | | | | |
| Sat 25/09/21 | Goole v Maine Road | 4-0 | | | | | |
| Sat 02/10/21 | New Mills v Maine Road | 2-0 | | | | | |
| Tue 05/10/21 | Bury AFC v Maine Road | 4-1 | | | | | |
| Sat 23/10/21 | Maine Road v Cammell Laird 1907 * | 5-0 | | | | | |
| Sat 30/10/21 | Maine Road v Cheadle Heath Nomads | 3-1 | | | | | |
| Sat 06/11/21 | Brocton v Maine Road | 3-2 | | | | | |
| Wed 10/11/21 | Barnton v Maine Road | 0-4 | | | | | |
| Sat 20/11/21 | FC Isle of Man v Maine Road | 2-2 | | | |  | |
| Sat 04/12/21 | Maine Road v Abbey Hey | 0-4 | | | | | |
| Sat 08/01/22 | Maine Road v Abbey Hulton United | - | | | | | |
| Sat 15/01/22 | Cheadle Town v Maine Road | 3-3 | | | | | |
| Sat 22/01/22 | Wythenshawe Amateurs v Maine Road | 2-1 | | | | | |
| Mon 24/01/22 | Maine Road v Alsager Town | 4-0 | | | | | |
| Sat 29/01/22 | Maine Road v Brocton | 0-0 | | | | | |
| Tue 01/02/22 | Stafford Town v Maine Road | 0-2 | | | | | |
| Tue 08/02/22 | Sandbach United v Maine Road | 1-2 | | | | | |
| Fri 18/02/22 | St Martins v Maine Road | 0-7 | | | | | |
| Sat 26/02/22 | Maine Road v Stockport Town | 2-1 | | | | | |
| Sat 12/03/22 | Rocester v Maine Road | 1-4 | | | | | |
| Sat 26/03/22 | Cheadle Heath Nomads v Maine Road | 4-1 | | | | | |
| Mon 28/03/22 | Maine Road v Abbey Hulton United | 4-0 | | | | | |
| Thu 31/03/22 | Ellesmere Rangers v Maine Road | 3-5 | | | | | |
| Sat 02/04/22 | Maine Road v Barnton | 2-1 | | | | | |
