| Sat 28/08/21 | Barnoldswick Town v Macclesfield | 1-2 | | | | | |
| Mon 30/08/21 | Macclesfield v Congleton Town | 1-0 | | | | | |
| Sat 04/09/21 | Ashton Athletic v Macclesfield | 1-1 | | | | | |
| Mon 20/09/21 | Longridge Town v Macclesfield | 4-2 | | | | | |
| Sat 02/10/21 | Macclesfield v Charnock Richard | 4-1 | | | | | |
| Tue 05/10/21 | Macclesfield v Northwich Victoria | 2-1 |  | | | | |
| Sat 09/10/21 | Wythenshawe Town v Macclesfield | 0-1 | | | | | |
| Sat 16/10/21 | Squires Gate v Macclesfield | 0-0 | | | | | |
| Sat 23/10/21 | Macclesfield v Padiham | 3-0 | | | | | |
| Fri 29/10/21 | Lower Breck v Macclesfield | 1-3 | | | | | |
| Sat 06/11/21 | Macclesfield v Runcorn Town | 2-2 | | | | | |
| Tue 09/11/21 | AFC Liverpool v Macclesfield | 1-2 | | | | | |
| Sat 13/11/21 | Skelmersdale United v Macclesfield | 0-0 | | | | | |
| Sat 27/11/21 | Northwich Victoria v Macclesfield | 3-4 | | | | | |
| Sat 04/12/21 | Macclesfield v Barnoldswick Town | 2-0 | | | | | |
| Sat 11/12/21 | Macclesfield v Squires Gate | 1-0 | | | | | |
| Fri 14/01/22 | Litherland REMYCA v Macclesfield | 1-2 | | | | | |
| Sat 22/01/22 | Charnock Richard v Macclesfield | 1-1 | | |  | | |
| Sat 29/01/22 | Macclesfield v Skelmersdale United | 3-1 | | | | | |
| Sat 05/02/22 | Padiham v Macclesfield | - | | | | | |
| Tue 08/02/22 | Irlam v Macclesfield | 2-2 | | | | | |
| Sat 12/02/22 | Macclesfield v Lower Breck | 4-0 | | | | | |
| Sat 19/02/22 | Burscough v Macclesfield | 0-4 | | | | | |
| Tue 22/02/22 | Vauxhall Motors v Macclesfield | 0-6 | | | | | |
| Sat 26/02/22 | Runcorn Town v Macclesfield | 0-1 | | | | | |
| Sat 05/03/22 | Macclesfield v Longridge Town | 3-1 | | | | | |
| Tue 08/03/22 | Padiham v Macclesfield | 0-2 | | | | | |
| Sat 12/03/22 | Macclesfield v Ashton Athletic | 4-0 | | | | | |
| Sat 26/03/22 | Congleton Town v Macclesfield | 1-3 | | | | | |
| Sat 02/04/22 | Macclesfield v AFC Liverpool | 4-2 | | | | | |
| Mon 02/05/22 | Skelmersdale United v Macclesfield | 3-2 | | | | | |
