| Round 1 |
| Saturday, 25 September 2021 |
| 1 | Didsbury Toc H 3rd XV | v | Bye |
| 2 | Stockport 3rd XV | v | Bye |
| 3 | Northwich 3rd XV | v | Bye |
| 4 | Widnes 3rd XV | v | Bye |
| 5 | Hope Valley | v | Bye |
| 6 | Marple 2nd XV | v | Bye |
| 7 | Congleton 2nd XV | v | Bye |
| 8 | Old Bedians 2nd XV | v | Bye |
| 9 | Macclesfield 4th XV | v | Bye |
| 10 | Bowdon 3rd XV | v | Bye |
| 11 | Bury 2nd XV | v | Bye |
| 12 | Burnage 3rd XV | v | Bye |
| 13 | Ashton-Under-Lyne 2nd XV | v | Bye |
| 14 | Glossop 3rd XV | v | Bye |
| 15 | Aspull 3rd XV | v | Bye |
| 16 | Southport 3rd XV | v | Bye |
| 17 | New Brighton 2nd XV | v | Bye |
| 18 | Ellesmere Port 2nd XV | v | Bye |
| 19 | Fleetwood 3rd XV | v | Bye |
| 20 | Bolton 3rd XV | v | Bye |
| 21 | Winnington Park 3rd XV | v | Bye |
| 22 | Preston Grasshoppers 6th XV | v | Bye |
| 23 | Preston Grasshoppers 5th XV | v | Bye |
| 24 | Vale of Lune 3rd XV | v | Bye |
| 25 | Ormskirk 3rd XV | v | Bye |
| 26 | West Park (St Helens) 3rd XV | v | Bye |
| 27 | Liverpool St Helens 3rd XV | v | Bye |
| 28 | Hawcoat Park 'A' Team (2nd XV) | v | Bye |
| 29 | Orrell 3rd XV | Away Walkover | Colne & Nelson 2nd XV |
| 30 | Moore 2nd XV | v | Bye |
| 31 | Garstang Blues (2nd XV) | v | Bye |
| 32 | Clitheroe 2nd XV | v | Bye |
| Round 2 |
| Saturday, 9 October 2021 |
| Didsbury Toc H 3rd XV | 12 | 47 | Stockport 3rd XV |
| Northwich 3rd XV | Home Walkover | Widnes 3rd XV |
| Congleton 2nd XV | Home Walkover | Old Bedians 2nd XV |
| Macclesfield 4th XV | 77 | 7 | Bowdon 3rd XV |
| Bury 2nd XV | 19 | 40 | Burnage 3rd XV |
| Ashton-Under-Lyne 2nd XV | Home Walkover | Glossop 3rd XV |
| Aspull 3rd XV | 45 | 20 | Southport 3rd XV |
| New Brighton 2nd XV | 12 | 22 | Ellesmere Port 2nd XV |
| Fleetwood 3rd XV | Away Walkover | Bolton 3rd XV |
| Winnington Park 3rd XV | Home Walkover | Preston Grasshoppers 6th XV |
| Preston Grasshoppers 5th XV | 11 | 31 | Vale of Lune 3rd XV |
| Ormskirk 3rd XV | 33 | 31 | West Park (St Helens) 3rd XV |
| Hawcoat Park 'A' Team (2nd XV) | v | Bye |
| Garstang Blues (2nd XV) | 5 | 38 | Clitheroe 2nd XV |
| Saturday, 16 October 2021 |
| Hope Valley | 59 | 24 | Marple 2nd XV |
| Saturday, 23 October 2021 |
| Colne & Nelson 2nd XV | 60 | 15 | Moore 2nd XV |
| Round 3 |
| Saturday, 6 November 2021 |
| Stockport 3rd XV | Home Walkover | Northwich 3rd XV |
| Hope Valley | Home Walkover | Congleton 2nd XV |
| Macclesfield 4th XV | 19 | 13 | Burnage 3rd XV |
| Ashton-Under-Lyne 2nd XV | 45 | 14 | Aspull 3rd XV |
| Ellesmere Port 2nd XV | 27 | 10 | Bolton 3rd XV |
| Winnington Park 3rd XV | 8 | 57 | Vale of Lune 3rd XV |
| Ormskirk 3rd XV | Home Walkover | Hawcoat Park 'A' Team (2nd XV) |
| Colne & Nelson 2nd XV | 15 | 12 | Clitheroe 2nd XV |
| Round 4 |
| Saturday, 5 February 2022 |
| Ellesmere Port 2nd XV | 15 | 20 | Ormskirk 3rd XV |
| Colne & Nelson 2nd XV | 0 | 12 | Ashton-Under-Lyne 2nd XV |
| Saturday, 12 February 2022 |
| Stockport 3rd XV | 12 | 0 | Hope Valley |
| Macclesfield 4th XV | 13 | 39 | Vale of Lune 3rd XV |
| Round 5 |
| Saturday, 26 February 2022 |
| Stockport 3rd XV | 17 | 25 | Ormskirk 3rd XV |
| Vale of Lune 3rd XV | 30 | 18 | Ashton-Under-Lyne 2nd XV |
| Round 6 |
| Saturday, 7 May 2022 |
| Ormskirk 3rd XV | 38 | 31 | Vale of Lune 3rd XV |