| Sat 23/10/21 | Prestwich Heys v Penrith | 4-2 | | | | | |
| Tue 26/10/21 | Prestwich Heys v AFC Liverpool | 1-0 | | | | | |
| Sat 30/10/21 | Prestwich Heys v Longridge Town | 2-4 | | |  | | |
| Sat 06/11/21 | Burscough v Prestwich Heys | 1-2 | | | | | |
| Tue 09/11/21 | Prestwich Heys v Runcorn Town | 3-2 | | | | | |
| Sat 27/11/21 | Congleton Town v Prestwich Heys | 2-0 | | | | | |
| Tue 14/12/21 | Prestwich Heys v Vauxhall Motors | 3-1 | | | | | |
| Sat 18/12/21 | Prestwich Heys v Harborough Town | 1-7 | | | | | |
| Mon 03/01/22 | Prestwich Heys v Macclesfield | 1-0 | | | | | |
| Tue 11/01/22 | Irlam v Prestwich Heys | 1-4 | | | | | |
| Sat 15/01/22 | Prestwich Heys v Skelmersdale United | 2-3 | | | | | |
| Sat 22/01/22 | Prestwich Heys v Wythenshawe Town | 1-1 | | | | | |
| Tue 25/01/22 | Runcorn Town v Prestwich Heys | 1-1 | | | | | |
| Sat 29/01/22 | Squires Gate v Prestwich Heys | 0-0 | | | | |  |
| Tue 01/02/22 | Prestwich Heys v Avro | 0-1 | | | | | |
| Sat 05/02/22 | Winsford United v Prestwich Heys | 5-0 | | | | | |
| Sat 26/02/22 | Northwich Victoria v Prestwich Heys | 0-1 | | | | | |
| Tue 01/03/22 | Prestwich Heys v Ashton Athletic | 1-2 | | | | | |
| Sat 05/03/22 | Prestwich Heys v Burscough | 1-1 | | | | | |
| Wed 09/03/22 | Longridge Town v Prestwich Heys | 3-2 | | | | | |
| Sat 12/03/22 | Lower Breck v Prestwich Heys | 3-3 | | | | | |
| Sat 19/03/22 | Charnock Richard v Prestwich Heys | 1-2 | | | | | |
| Tue 22/03/22 | Prestwich Heys v Litherland REMYCA | 0-1 | | | | | |
| Sat 26/03/22 | AFC Liverpool v Prestwich Heys | 3-1 | | | | | |
| Tue 05/04/22 | Bury AFC v Prestwich Heys | 4-1 | | | | | |
