| Saturday, 4 September 2021 |
| Kendal 2nd XV | 7 | 39 | Birkenhead Park Wanderers (2nd XV) |
| Stockport 2nd XV | 34 | 24 | Firwood Waterloo 2nd XV |
| Vale of Lune 2nd XV | 16 | 17 | Sedgley Park 3rd XV |
| Wilmslow 2nd XV | 31 | 25 | Chester 3rd XV |
| Saturday, 11 September 2021 |
| Firwood Waterloo 2nd XV | 59 | 0 | Glossop 2nd XV |
| Stockport 2nd XV | 12 | 39 | Wirral 2nd XV |
| Vale of Lune 2nd XV | 12 | 30 | Kendal 2nd XV |
| Saturday, 18 September 2021 |
| Birkenhead Park Wanderers (2nd XV) | 12 | 43 | Firwood Waterloo 2nd XV |
| Chester 3rd XV | 24 | 14 | Stockport 2nd XV |
| Glossop 2nd XV | 27 | 17 | Wilmslow 2nd XV |
| Kendal 2nd XV | 93 | 0 | Holmes Chapel |
| Wirral 2nd XV | 12 | 7 | Sedgley Park 3rd XV |
| Saturday, 25 September 2021 |
| Sedgley Park 3rd XV | 38 | 0 | Chester 3rd XV |
| Vale of Lune 2nd XV | 28 | 38 | Wirral 2nd XV |
| Saturday, 2 October 2021 |
| Chester 3rd XV | 12 | 14 | Vale of Lune 2nd XV |
| Glossop 2nd XV | 5 | 31 | Stockport 2nd XV |
| Holmes Chapel | 13 | 25 | Wilmslow 2nd XV |
| Kendal 2nd XV | 43 | 0 | Firwood Waterloo 2nd XV |
| Saturday, 9 October 2021 |
| Chester 3rd XV | 12 | 40 | Wirral 2nd XV |
| Saturday, 16 October 2021 |
| Birkenhead Park Wanderers (2nd XV) | 22 | 22 | Stockport 2nd XV |
| Sedgley Park 3rd XV | 15 | 19 | Glossop 2nd XV |
| Wilmslow 2nd XV | 29 | 29 | Firwood Waterloo 2nd XV |
| Saturday, 23 October 2021 |
| Holmes Chapel | 3 | 53 | Stockport 2nd XV |
| Kendal 2nd XV | 81 | 0 | Wilmslow 2nd XV |
| Vale of Lune 2nd XV | 35 | 19 | Glossop 2nd XV |
| Saturday, 30 October 2021 |
| Birkenhead Park Wanderers (2nd XV) | 22 | 37 | Vale of Lune 2nd XV |
| Chester 3rd XV | 15 | 64 | Kendal 2nd XV |
| Sedgley Park 3rd XV | 50 | 0 | Holmes Chapel |
| Saturday, 6 November 2021 |
| Firwood Waterloo 2nd XV | 71 | 5 | Holmes Chapel |
| Wirral 2nd XV | 21 | 12 | Kendal 2nd XV |
| Saturday, 13 November 2021 |
| Glossop 2nd XV | 8 | 33 | Wirral 2nd XV |
| Holmes Chapel | 17 | 13 | Vale of Lune 2nd XV |
| Wilmslow 2nd XV | 15 | 36 | Stockport 2nd XV |
| Friday, 19 November 2021 |
| Wirral 2nd XV | 8 | 3 | Birkenhead Park Wanderers (2nd XV) |
| Saturday, 20 November 2021 |
| Chester 3rd XV | 36 | 26 | Glossop 2nd XV |
| Sedgley Park 3rd XV | 36 | 7 | Wilmslow 2nd XV |
| Saturday, 27 November 2021 |
| Birkenhead Park Wanderers (2nd XV) | 31 | 0 | Chester 3rd XV |
| Firwood Waterloo 2nd XV | 50 | 19 | Sedgley Park 3rd XV |
| Holmes Chapel | 12 | 35 | Wirral 2nd XV |
| Stockport 2nd XV | 58 | 0 | Kendal 2nd XV |
| Vale of Lune 2nd XV | 31 | 24 | Wilmslow 2nd XV |
| Saturday, 4 December 2021 |
| Chester 3rd XV | 19 | 17 | Holmes Chapel |
| Glossop 2nd XV | Home Walkover | Kendal 2nd XV |
| Wilmslow 2nd XV | Postponed | Birkenhead Park Wanderers (2nd XV) |
| Wirral 2nd XV | 19 | 21 | Firwood Waterloo 2nd XV |
| Saturday, 11 December 2021 |
| Birkenhead Park Wanderers (2nd XV) | 8 | 0 | Glossop 2nd XV |
| Firwood Waterloo 2nd XV | 17 | 20 | Chester 3rd XV |
| Kendal 2nd XV | 22 | 29 | Sedgley Park 3rd XV |
| Vale of Lune 2nd XV | 5 | 31 | Stockport 2nd XV |
| Wilmslow 2nd XV | 12 | 14 | Wirral 2nd XV |
| Saturday, 8 January 2022 |
| Firwood Waterloo 2nd XV | 7 | 0 | Birkenhead Park Wanderers (2nd XV) |
| Stockport 2nd XV | 26 | 19 | Chester 3rd XV |
| Saturday, 15 January 2022 |
| Birkenhead Park Wanderers (2nd XV) | 19 | 36 | Wilmslow 2nd XV |
| Chester 3rd XV | 36 | 32 | Sedgley Park 3rd XV |
| Holmes Chapel | 0 | 19 | Firwood Waterloo 2nd XV |
| Wirral 2nd XV | 47 | 3 | Vale of Lune 2nd XV |
| Saturday, 22 January 2022 |
| Firwood Waterloo 2nd XV | 81 | 10 | Kendal 2nd XV |
| Sedgley Park 3rd XV | 5 | 10 | Birkenhead Park Wanderers (2nd XV) |
| Stockport 2nd XV | 24 | 22 | Glossop 2nd XV |
| Wilmslow 2nd XV | 31 | 12 | Holmes Chapel |
| Saturday, 29 January 2022 |
| Firwood Waterloo 2nd XV | Home Walkover | Wilmslow 2nd XV |
| Kendal 2nd XV | 32 | 19 | Wirral 2nd XV |
| Stockport 2nd XV | 57 | 0 | Birkenhead Park Wanderers (2nd XV) |
| Saturday, 5 February 2022 |
| Glossop 2nd XV | 22 | 12 | Holmes Chapel |
| Sedgley Park 3rd XV | 0 | 5 | Wirral 2nd XV |
| Wilmslow 2nd XV | 25 | 7 | Birkenhead Park Wanderers (2nd XV) |
| Saturday, 12 February 2022 |
| Birkenhead Park Wanderers (2nd XV) | 22 | 19 | Sedgley Park 3rd XV |
| Glossop 2nd XV | 12 | 7 | Vale of Lune 2nd XV |
| Stockport 2nd XV | Home Walkover | Holmes Chapel |
| Wilmslow 2nd XV | 15 | 27 | Kendal 2nd XV |
| Wirral 2nd XV | Home Walkover | Chester 3rd XV |
| Saturday, 19 February 2022 |
| Firwood Waterloo 2nd XV | 5 | 40 | Stockport 2nd XV |
| Kendal 2nd XV | Home Walkover | Chester 3rd XV |
| Wilmslow 2nd XV | Postponed | Glossop 2nd XV |
| Saturday, 26 February 2022 |
| Holmes Chapel | 19 | 26 | Sedgley Park 3rd XV |
| Vale of Lune 2nd XV | 29 | 24 | Chester 3rd XV |
| Wilmslow 2nd XV | 0 | 5 | Glossop 2nd XV |
| Saturday, 5 March 2022 |
| Sedgley Park 3rd XV | 20 | 30 | Firwood Waterloo 2nd XV |
| Stockport 2nd XV | 92 | 12 | Wilmslow 2nd XV |
| Vale of Lune 2nd XV | 22 | 5 | Holmes Chapel |
| Wirral 2nd XV | Home Walkover | Glossop 2nd XV |
| Saturday, 12 March 2022 |
| Birkenhead Park Wanderers (2nd XV) | 0 | 28 | Wirral 2nd XV |
| Glossop 2nd XV | 38 | 22 | Chester 3rd XV |
| Holmes Chapel | Home Walkover | Kendal 2nd XV |
| Vale of Lune 2nd XV | 15 | 22 | Firwood Waterloo 2nd XV |
| Wilmslow 2nd XV | 14 | 17 | Sedgley Park 3rd XV |
| Saturday, 19 March 2022 |
| Birkenhead Park Wanderers (2nd XV) | 62 | 10 | Holmes Chapel |
| Firwood Waterloo 2nd XV | 48 | 19 | Vale of Lune 2nd XV |
| Sedgley Park 3rd XV | 14 | 35 | Stockport 2nd XV |
| Saturday, 26 March 2022 |
| Chester 3rd XV | 25 | 32 | Birkenhead Park Wanderers (2nd XV) |
| Glossop 2nd XV | 27 | 21 | Sedgley Park 3rd XV |
| Kendal 2nd XV | 36 | 31 | Stockport 2nd XV |
| Wilmslow 2nd XV | Away Walkover | Vale of Lune 2nd XV |
| Wirral 2nd XV | Home Walkover | Holmes Chapel |
| Saturday, 2 April 2022 |
| Firwood Waterloo 2nd XV | 15 | 31 | Wirral 2nd XV |
| Glossop 2nd XV | 7 | 31 | Kendal 2nd XV |
| Holmes Chapel | 14 | 17 | Chester 3rd XV |
| Stockport 2nd XV | 40 | 14 | Sedgley Park 3rd XV |
| Vale of Lune 2nd XV | 38 | 10 | Birkenhead Park Wanderers (2nd XV) |
| Saturday, 9 April 2022 |
| Chester 3rd XV | 27 | 66 | Firwood Waterloo 2nd XV |
| Glossop 2nd XV | Home Walkover | Birkenhead Park Wanderers (2nd XV) |
| Sedgley Park 3rd XV | Away Walkover | Kendal 2nd XV |
| Stockport 2nd XV | 66 | 15 | Vale of Lune 2nd XV |
| Wirral 2nd XV | 90 | 7 | Wilmslow 2nd XV |
| Saturday, 23 April 2022 |
| Birkenhead Park Wanderers (2nd XV) | 65 | 14 | Kendal 2nd XV |
| Chester 3rd XV | 45 | 13 | Wilmslow 2nd XV |
| Holmes Chapel | 27 | 7 | Glossop 2nd XV |
| Sedgley Park 3rd XV | 56 | 8 | Vale of Lune 2nd XV |
| Wirral 2nd XV | 76 | 0 | Stockport 2nd XV |
| Saturday, 30 April 2022 |
| Glossop 2nd XV | 14 | 73 | Firwood Waterloo 2nd XV |
| Holmes Chapel | Home Walkover | Birkenhead Park Wanderers (2nd XV) |
| Kendal 2nd XV | 22 | 53 | Vale of Lune 2nd XV |