| Saturday, 4 September 2021 |
| Bowdon 2nd XV | 33 | 7 | Eccles 2nd XV |
| Broughton Park 2nd XV | 29 | 20 | Anselmians 2nd XV |
| Crewe & Nantwich 2nd XV | 14 | 39 | Warrington 2nd XV |
| Saturday, 11 September 2021 |
| Altrincham Kersal Cougars (2nd XV) | 20 | 31 | Warrington 2nd XV |
| Anselmians 2nd XV | Home Walkover | Bowdon 2nd XV |
| Didsbury Toc H 2nd XV | 0 | 25 | Broughton Park 2nd XV |
| Eccles 2nd XV | 67 | 0 | Manchester 2nd XV |
| Knutsford | 17 | 20 | Crewe & Nantwich 2nd XV |
| Saturday, 18 September 2021 |
| Broughton Park 2nd XV | 57 | 10 | Liverpool University Veterinarians |
| Crewe & Nantwich 2nd XV | 47 | 34 | Altrincham Kersal Cougars (2nd XV) |
| Manchester 2nd XV | 19 | 26 | Anselmians 2nd XV |
| Saturday, 25 September 2021 |
| Didsbury Toc H 2nd XV | 50 | 5 | Manchester 2nd XV |
| Eccles 2nd XV | 26 | 5 | Warrington 2nd XV |
| Knutsford | 7 | 31 | Broughton Park 2nd XV |
| Saturday, 2 October 2021 |
| Altrincham Kersal Cougars (2nd XV) | 34 | 19 | Eccles 2nd XV |
| Bowdon 2nd XV | 12 | 26 | Knutsford |
| Manchester 2nd XV | 5 | 31 | Liverpool University Veterinarians |
| Warrington 2nd XV | 31 | 5 | Anselmians 2nd XV |
| Saturday, 9 October 2021 |
| Knutsford | 21 | 10 | Liverpool University Veterinarians |
| Saturday, 16 October 2021 |
| Anselmians 2nd XV | 31 | 17 | Altrincham Kersal Cougars (2nd XV) |
| Broughton Park 2nd XV | 45 | 12 | Crewe & Nantwich 2nd XV |
| Didsbury Toc H 2nd XV | 7 | 24 | Warrington 2nd XV |
| Knutsford | 25 | 10 | Manchester 2nd XV |
| Saturday, 23 October 2021 |
| Altrincham Kersal Cougars (2nd XV) | 15 | 43 | Didsbury Toc H 2nd XV |
| Bowdon 2nd XV | 0 | 95 | Broughton Park 2nd XV |
| Crewe & Nantwich 2nd XV | Home Walkover | Eccles 2nd XV |
| Warrington 2nd XV | 20 | 17 | Liverpool University Veterinarians |
| Saturday, 30 October 2021 |
| Anselmians 2nd XV | 26 | 26 | Eccles 2nd XV |
| Broughton Park 2nd XV | 36 | 15 | Manchester 2nd XV |
| Knutsford | 12 | 41 | Warrington 2nd XV |
| Saturday, 13 November 2021 |
| Altrincham Kersal Cougars (2nd XV) | 21 | 29 | Knutsford |
| Crewe & Nantwich 2nd XV | 7 | 21 | Anselmians 2nd XV |
| Eccles 2nd XV | 15 | 23 | Didsbury Toc H 2nd XV |
| Manchester 2nd XV | 52 | 33 | Bowdon 2nd XV |
| Saturday, 20 November 2021 |
| Broughton Park 2nd XV | 24 | 20 | Warrington 2nd XV |
| Didsbury Toc H 2nd XV | 13 | 12 | Anselmians 2nd XV |
| Manchester 2nd XV | 41 | 20 | Crewe & Nantwich 2nd XV |
| Saturday, 27 November 2021 |
| Anselmians 2nd XV | 22 | 17 | Liverpool University Veterinarians |
| Crewe & Nantwich 2nd XV | 5 | 27 | Didsbury Toc H 2nd XV |
| Eccles 2nd XV | 58 | 24 | Knutsford |
| Warrington 2nd XV | Home Walkover | Bowdon 2nd XV |
| Saturday, 4 December 2021 |
| Bowdon 2nd XV | 8 | 12 | Altrincham Kersal Cougars (2nd XV) |
| Liverpool University Veterinarians | 10 | 10 | Didsbury Toc H 2nd XV |
| Manchester 2nd XV | 12 | 45 | Warrington 2nd XV |
| Saturday, 11 December 2021 |
| Altrincham Kersal Cougars (2nd XV) | 12 | 36 | Manchester 2nd XV |
| Crewe & Nantwich 2nd XV | 29 | 12 | Liverpool University Veterinarians |
| Didsbury Toc H 2nd XV | 46 | 0 | Knutsford |
| Eccles 2nd XV | 7 | 34 | Broughton Park 2nd XV |
| Saturday, 8 January 2022 |
| Altrincham Kersal Cougars (2nd XV) | 31 | 0 | Crewe & Nantwich 2nd XV |
| Anselmians 2nd XV | 8 | 0 | Manchester 2nd XV |
| Didsbury Toc H 2nd XV | 57 | 17 | Bowdon 2nd XV |
| Saturday, 15 January 2022 |
| Bowdon 2nd XV | 39 | 14 | Liverpool University Veterinarians |
| Broughton Park 2nd XV | 52 | 19 | Knutsford |
| Manchester 2nd XV | 22 | 22 | Didsbury Toc H 2nd XV |
| Warrington 2nd XV | 39 | 0 | Eccles 2nd XV |
| Saturday, 22 January 2022 |
| Anselmians 2nd XV | 33 | 13 | Warrington 2nd XV |
| Eccles 2nd XV | 24 | 27 | Altrincham Kersal Cougars (2nd XV) |
| Knutsford | 56 | 38 | Bowdon 2nd XV |
| Liverpool University Veterinarians | 14 | 25 | Manchester 2nd XV |
| Saturday, 29 January 2022 |
| Altrincham Kersal Cougars (2nd XV) | 10 | 29 | Anselmians 2nd XV |
| Crewe & Nantwich 2nd XV | 7 | 52 | Broughton Park 2nd XV |
| Liverpool University Veterinarians | 7 | 12 | Eccles 2nd XV |
| Manchester 2nd XV | 28 | 31 | Knutsford |
| Warrington 2nd XV | 14 | 7 | Didsbury Toc H 2nd XV |
| Saturday, 5 February 2022 |
| Liverpool University Veterinarians | 12 | 67 | Altrincham Kersal Cougars (2nd XV) |
| Saturday, 12 February 2022 |
| Broughton Park 2nd XV | Home Walkover | Bowdon 2nd XV |
| Crewe & Nantwich 2nd XV | 14 | 29 | Eccles 2nd XV |
| Didsbury Toc H 2nd XV | 27 | 0 | Altrincham Kersal Cougars (2nd XV) |
| Knutsford | 0 | 8 | Anselmians 2nd XV |
| Liverpool University Veterinarians | 15 | 42 | Warrington 2nd XV |
| Saturday, 19 February 2022 |
| Altrincham Kersal Cougars (2nd XV) | Home Walkover | Liverpool University Veterinarians |
| Broughton Park 2nd XV | 45 | 7 | Manchester 2nd XV |
| Crewe & Nantwich 2nd XV | 28 | 20 | Bowdon 2nd XV |
| Eccles 2nd XV | Away Walkover | Anselmians 2nd XV |
| Warrington 2nd XV | Home Walkover | Knutsford |
| Saturday, 26 February 2022 |
| Altrincham Kersal Cougars (2nd XV) | 5 | 26 | Broughton Park 2nd XV |
| Liverpool University Veterinarians | 45 | 0 | Bowdon 2nd XV |
| Saturday, 5 March 2022 |
| Anselmians 2nd XV | 40 | 3 | Crewe & Nantwich 2nd XV |
| Bowdon 2nd XV | 7 | 70 | Manchester 2nd XV |
| Didsbury Toc H 2nd XV | 57 | 5 | Eccles 2nd XV |
| Knutsford | 26 | 13 | Altrincham Kersal Cougars (2nd XV) |
| Liverpool University Veterinarians | Away Walkover | Broughton Park 2nd XV |
| Saturday, 12 March 2022 |
| Anselmians 2nd XV | Home Walkover | Didsbury Toc H 2nd XV |
| Crewe & Nantwich 2nd XV | 22 | 12 | Manchester 2nd XV |
| Eccles 2nd XV | 5 | 5 | Liverpool University Veterinarians |
| Warrington 2nd XV | 20 | 24 | Broughton Park 2nd XV |
| Saturday, 19 March 2022 |
| Bowdon 2nd XV | 38 | 19 | Didsbury Toc H 2nd XV |
| Liverpool University Veterinarians | 35 | 0 | Crewe & Nantwich 2nd XV |
| Saturday, 26 March 2022 |
| Broughton Park 2nd XV | 79 | 10 | Altrincham Kersal Cougars (2nd XV) |
| Didsbury Toc H 2nd XV | 90 | 20 | Crewe & Nantwich 2nd XV |
| Knutsford | 29 | 38 | Eccles 2nd XV |
| Liverpool University Veterinarians | 14 | 30 | Anselmians 2nd XV |
| Warrington 2nd XV | 62 | 14 | Bowdon 2nd XV |
| Saturday, 2 April 2022 |
| Altrincham Kersal Cougars (2nd XV) | 5 | 27 | Bowdon 2nd XV |
| Anselmians 2nd XV | 45 | 10 | Knutsford |
| Didsbury Toc H 2nd XV | 54 | 17 | Liverpool University Veterinarians |
| Warrington 2nd XV | 42 | 15 | Manchester 2nd XV |
| Saturday, 9 April 2022 |
| Bowdon 2nd XV | 52 | 12 | Crewe & Nantwich 2nd XV |
| Broughton Park 2nd XV | Home Walkover | Eccles 2nd XV |
| Knutsford | 12 | 44 | Didsbury Toc H 2nd XV |
| Manchester 2nd XV | 55 | 20 | Altrincham Kersal Cougars (2nd XV) |
| Saturday, 23 April 2022 |
| Anselmians 2nd XV | 12 | 24 | Broughton Park 2nd XV |
| Eccles 2nd XV | 14 | 34 | Bowdon 2nd XV |
| Liverpool University Veterinarians | 22 | 39 | Knutsford |
| Warrington 2nd XV | 85 | 21 | Crewe & Nantwich 2nd XV |
| Saturday, 30 April 2022 |
| Anselmians 2nd XV | 7 | 7 | Bowdon 2nd XV |
| Broughton Park 2nd XV | 5 | 102 | Didsbury Toc H 2nd XV |
| Crewe & Nantwich 2nd XV | 12 | 17 | Knutsford |
| Manchester 2nd XV | 50 | 15 | Eccles 2nd XV |
| Warrington 2nd XV | Home Walkover | Altrincham Kersal Cougars (2nd XV) |