| Sat 31/07/21 | St Helens Town v Atherton LR | 2-5 | | | | | |
| Wed 04/08/21 | Garstang v St Helens Town | 2-2 | | | | | |
| Sat 07/08/21 | St Helens Town v Pilkington | 1-4 | | | | | |
| Sat 14/08/21 | Cleator Moor Celtic v St Helens Town | 10-0 | | | | | |
| Thu 19/08/21 | St Helens Town v AFC Blackpool | 1-3 | | | | | |
| Sat 21/08/21 | Steeton v St Helens Town | 1-1 | | | | | |
| Sat 28/08/21 | St Helens Town v Daisy Hill | 1-8 |  | | | | |
| Mon 30/08/21 | St Helens Town v South Liverpool * | 1-3 | | | | | |
| Sat 04/09/21 | Nelson v St Helens Town | 2-2 | | | | | |
| Thu 09/09/21 | St Helens Town v Ashton Town | 0-3 | | | | | |
| Sat 11/09/21 | St Helens Town v Cheadle Heath Nomads | 0-4 | | | | | |
| Sat 18/09/21 | Ilkley Town v St Helens Town | 3-2 | | | | | |
| Sat 25/09/21 | Campion v St Helens Town | 7-1 | | | | | |
| Sat 02/10/21 | St Helens Town v Bacup Borough | 1-2 | | | | |  |
| Sat 09/10/21 | Chadderton v St Helens Town | 3-2 | | | | | |
| Sat 16/10/21 | St Helens Town v Bury AFC | 0-5 | | | | | |
| Sat 30/10/21 | Golcar United v St Helens Town | 2-1 | | | | | |
| Sat 06/11/21 | St Helens Town v AFC Darwen | 2-7 | | | | | |
| Thu 11/11/21 | St Helens Town v Holker Old Boys | 1-1 | | | | | |
| Sat 20/11/21 | Daisy Hill v St Helens Town | 3-2 | | | | | |
| Thu 25/11/21 | St Helens Town v Garstang | 1-4 | | | | | |
| Sat 27/11/21 | St Helens Town v Golcar United | 3-2 | | | | | |
| Sat 04/12/21 | AFC Darwen v St Helens Town | 2-3 | | | | | |
| Sat 11/12/21 | St Helens Town v Campion | 2-6 | | | | | |
| Sat 18/12/21 | Atherton LR v St Helens Town * | 1-2 | | | | | |
| Mon 27/12/21 | Ashton Town v St Helens Town | 2-1 | | | | | |
| Sat 08/01/22 | St Helens Town v Cleator Moor Celtic | 4-5 | | | | | |
| Fri 04/02/22 | South Liverpool v St Helens Town | 4-1 | | | | | |
| Sat 12/02/22 | Pilkington v St Helens Town | 4-2 | | | | | |
| Sat 19/02/22 | St Helens Town v Steeton | 4-1 | | | | | |
| Thu 24/02/22 | St Helens Town v Bacup Borough | 6-1 | | | | | |
| Sat 05/03/22 | Bacup Borough v St Helens Town | 6-1 | | | | | |
| Thu 10/03/22 | St Helens Town v AFC Darwen | 2-3 | | | | | |
| Sat 12/03/22 | St Helens Town v Nelson | 3-4 | | |  | | |
| Wed 16/03/22 | Garstang v St Helens Town | 1-4 | | | | | |
| Sat 19/03/22 | St Helens Town v Chadderton | 2-5 | | | | | |
| Sun 27/03/22 | Bury AFC v St Helens Town | 4-0 | | | | | |
| Wed 30/03/22 | Pilkington v St Helens Town | 1-3 | | | | | |
| Tue 12/04/22 | Skelmersdale United v St Helens Town | 6-1 | | | | | |
