| 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 21/08/21 | Maine Road v Sandbach United * | 1-2 | | | | | |
| Sat 28/08/21 | Maine Road v Stafford Town * | 4-1 |  | | | | |
| Mon 30/08/21 | West Didsbury & Chorlton v Maine Road * | 3-2 | | | | | |
| Sat 04/09/21 | Abbey Hulton United v Maine Road | 3-2 | | | | | |
| Mon 06/09/21 | Maine Road v Cheadle Town | 0-2 | | | | | |
| 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 | | | |  | |
| Tue 05/10/21 | Bury AFC v Maine Road | 4-1 | | | | | |
| Sat 09/10/21 | Maine Road v St Martins | 7-0 | | | | | |
| Sat 16/10/21 | Eccleshall v Maine Road | 0-4 | | | | | |
| 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 13/11/21 | Stockport Town v Maine Road | 2-1 | | | | | |
| Sat 20/11/21 | FC Isle of Man v Maine Road | 2-2 | | | | | |
| Sat 27/11/21 | Maine Road v Eccleshall | 4-0 | | | | | |
| Sat 04/12/21 | Maine Road v Abbey Hey | 0-4 | | | | | |
| Sat 08/01/22 | Maine Road v Abbey Hulton United | - | | | | | |
| Sat 22/01/22 | Wythenshawe Amateurs v Maine Road * | 2-1 | | | | | |
| Sat 29/01/22 | Maine Road v Brocton | 0-0 | | | | | |
| Tue 01/02/22 | Stafford Town v Maine Road | 0-2 | | | | | |
| Sat 05/02/22 | Cammell Laird 1907 v Maine Road | 2-7 | | | | | |
| 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 | | | | | |
| Mon 14/03/22 | Maine Road v New Mills | 3-3 | | | | | |
| Sat 19/03/22 | Maine Road v West Didsbury & Chorlton | 1-3 | | | | |  |
| Sat 26/03/22 | Cheadle Heath Nomads v Maine Road | 4-1 | | | | | |
| Thu 31/03/22 | Ellesmere Rangers v Maine Road | 3-5 | | |  | | |
| Sat 02/04/22 | Maine Road v Barnton | 2-1 | | | | | |
| Mon 04/04/22 | Maine Road v West Didsbury & Chorlton | 1-1 | | | | | |
