| 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 | | | | | |
| Sat 02/10/21 | Longridge Town v Wythenshawe Town | 0-0 | | | | | |
| 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 | | | | | |
| 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 | | | | | |
| Sat 18/12/21 | Vauxhall Motors v Wythenshawe Town | 3-0 | | | | | |
| 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 | | | | | |
| Sat 22/01/22 | Prestwich Heys v Wythenshawe Town | 1-1 | | | | | |
| Sat 29/01/22 | Wythenshawe Town v Runcorn Town | 7-0 | | | | | |
| Sat 05/02/22 | Wythenshawe Town v Skelmersdale United | 2-1 | | | | | |
| Sat 12/02/22 | Anstey Nomads v Wythenshawe Town | 1-1 | | | | | |
| Sat 26/02/22 | Avro v Wythenshawe Town | 0-2 |  | | | | |
| Tue 01/03/22 | Congleton Town v Wythenshawe Town | 1-1 | | | | | |
| Sat 05/03/22 | Litherland REMYCA v Wythenshawe Town | 0-1 | | | | | |
| Tue 08/03/22 | Wythenshawe Town v Winsford United | 1-0 | | | | | |
| Sat 26/03/22 | Charnock Richard v Wythenshawe Town * | 1-4 | | | | | |
| Sat 02/04/22 | Wythenshawe Town v Squires Gate | 2-0 | | | | | |
| Tue 12/04/22 | Wythenshawe Town v Wythenshawe Amateurs | 1-3 | | | | | |
