| 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 28/08/21 | Wythenshawe Town v Lower Breck | 3-2 | | | | | |
| Sat 04/09/21 | Wythenshawe Town v Burscough | 2-2 | | | | | |
| Tue 07/09/21 | Irlam v Wythenshawe Town | 2-0 | | | | | |
| 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 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 | | | | | |
| Tue 18/01/22 | Wythenshawe Town v Ashton Athletic * | 4-0 | | | | | |
| 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 12/03/22 | Loughborough University v Wythenshawe Town | 2-0 | | | | | |
| Thu 17/03/22 | Lower Breck v Wythenshawe Town * | 1-4 | | | | | |
| Wed 23/03/22 | Barnoldswick Town v Wythenshawe Town * | 1-1 | | | | | |
| Tue 29/03/22 | Wythenshawe Town v Northwich Victoria * | 1-2 | | | | | |
| Sat 02/04/22 | Wythenshawe Town v Squires Gate * | 2-0 | | | | | |
