| Sat 31/07/21 | Ashton Athletic v Wythenshawe Town | 0-1 | | | | | |
| Wed 11/08/21 | Northwich Victoria v Wythenshawe Town | 3-1 |  | | | |  |
| Sat 14/08/21 | Wythenshawe Town v Vauxhall Motors | 5-0 | | | | | |
| Tue 17/08/21 | Runcorn Town v Wythenshawe Town | 1-1 | | | | | |
| Sat 21/08/21 | Wythenshawe Town v 1874 Northwich | 1-2 | | | | | |
| Sat 04/09/21 | Wythenshawe Town v Burscough | 2-2 | | | | | |
| Tue 07/09/21 | Irlam v Wythenshawe Town | 2-0 | | | | | |
| Sat 11/09/21 | Litherland REMYCA v Wythenshawe Town | 0-6 | | | | | |
| Tue 14/09/21 | Wythenshawe Town v Prestwich Heys | 4-1 | | | | | |
| Sat 18/09/21 | Skelmersdale United v Wythenshawe Town | 2-2 | | | | | |
| Sat 25/09/21 | Bacup Borough v Wythenshawe Town | 3-3 | | |  | | |
| Tue 28/09/21 | Wythenshawe Town v Congleton Town | 0-1 | | | | | |
| Sat 02/10/21 | Longridge Town v Wythenshawe Town | 0-0 | | | | | |
| Tue 05/10/21 | Winsford United v Wythenshawe Town | 0-1 | | | | | |
| Sat 09/10/21 | Wythenshawe Town v Macclesfield | 0-1 | | | | | |
| Tue 12/10/21 | Wythenshawe Town v Trafford | 2-3 | | | | | |
| Sat 16/10/21 | Wythenshawe Town v Litherland REMYCA | 5-0 | | | | | |
| Sat 23/10/21 | Seaham Red Star v Wythenshawe Town | 0-0 | | | | | |
| Tue 26/10/21 | Wythenshawe Town v Barnoldswick Town | 1-2 | | | | | |
| Fri 29/10/21 | AFC Liverpool v Wythenshawe Town * | 1-3 | | | | | |
| Sat 06/11/21 | Wythenshawe Town v Avro | 1-0 | | | | | |
| Tue 09/11/21 | Wythenshawe Town v Charnock Richard | 4-2 | | | | | |
| Sat 13/11/21 | Squires Gate v Wythenshawe Town | 2-2 | | | | | |
| Sat 20/11/21 | Holker Old Boys v Wythenshawe Town | 0-3 | | | | | |
| Tue 23/11/21 | Wythenshawe Town v Longridge Town | 5-1 | | | | | |
| Sat 27/11/21 | Padiham v Wythenshawe Town | 1-4 | | | | | |
| Sat 04/12/21 | Burscough v Wythenshawe Town | 5-1 | | | | | |
| Sat 11/12/21 | Wythenshawe Town v Billingham Synthonia | 3-0 | | | | | |
| Wed 15/12/21 | Wythenshawe Town v AFC Liverpool | 2-2 | | | | | |
| Mon 27/12/21 | Wythenshawe Town v Irlam | 1-0 | | | | | |
| Mon 03/01/22 | Lower Breck v Wythenshawe Town | 0-2 | | | | | |
| Sat 08/01/22 | Macclesfield v Wythenshawe Town | 2-4 | | | | | |
| Sat 15/01/22 | Consett v Wythenshawe Town | 1-2 | | | | | |
| Tue 18/01/22 | Wythenshawe Town v Ashton Athletic | 4-0 | | | | | |
| Sat 22/01/22 | Prestwich Heys v Wythenshawe Town | 1-1 | | | | | |
