| Saturday, 4 September 2021 |
| Bolton 2nd XV | 12 | 5 | Leigh 2nd XV |
| Rochdale 2nd XV | 18 | 3 | Chorley |
| Saturday, 11 September 2021 |
| Aspull 2nd XV | 28 | 31 | Fylde Saracens (3rd XV) |
| Leigh 2nd XV | 12 | 49 | Chorley |
| Saturday, 18 September 2021 |
| Fylde Saracens (3rd XV) | 12 | 17 | Southport 2nd XV |
| Preston Grasshoppers 3rd XV | 26 | 27 | Leyland Warriors |
| Saturday, 25 September 2021 |
| Aspull 2nd XV | 15 | 3 | Chorley |
| Southport 2nd XV | 57 | 5 | Bolton 2nd XV |
| Saturday, 2 October 2021 |
| Chorley | 23 | 28 | Southport 2nd XV |
| Leyland Warriors | 15 | 3 | Leigh 2nd XV |
| Preston Grasshoppers 3rd XV | 18 | 19 | Rochdale 2nd XV |
| Saturday, 16 October 2021 |
| Fylde Saracens (3rd XV) | 14 | 52 | Preston Grasshoppers 3rd XV |
| Saturday, 23 October 2021 |
| Bolton 2nd XV | Home Walkover | Fylde Saracens (3rd XV) |
| Leyland Warriors | 54 | 33 | Aspull 2nd XV |
| Preston Grasshoppers 3rd XV | 5 | 55 | Leigh 2nd XV |
| Saturday, 30 October 2021 |
| Aspull 2nd XV | 24 | 17 | Rochdale 2nd XV |
| Bolton 2nd XV | 29 | 5 | Preston Grasshoppers 3rd XV |
| Fylde Saracens (3rd XV) | 19 | 5 | Chorley |
| Southport 2nd XV | 17 | 25 | Leyland Warriors |
| Saturday, 13 November 2021 |
| Chorley | 30 | 10 | Bolton 2nd XV |
| Leigh 2nd XV | 38 | 19 | Aspull 2nd XV |
| Rochdale 2nd XV | 22 | 12 | Southport 2nd XV |
| Saturday, 20 November 2021 |
| Bolton 2nd XV | 17 | 31 | Aspull 2nd XV |
| Chorley | 14 | 47 | Preston Grasshoppers 3rd XV |
| Southport 2nd XV | 38 | 14 | Leigh 2nd XV |
| Saturday, 27 November 2021 |
| Preston Grasshoppers 3rd XV | 22 | 28 | Aspull 2nd XV |
| Saturday, 4 December 2021 |
| Bolton 2nd XV | Away Walkover | Leyland Warriors |
| Fylde Saracens (3rd XV) | 17 | 5 | Rochdale 2nd XV |
| Southport 2nd XV | 5 | 10 | Aspull 2nd XV |
| Saturday, 11 December 2021 |
| Bolton 2nd XV | 10 | 38 | Rochdale 2nd XV |
| Preston Grasshoppers 3rd XV | 7 | 15 | Southport 2nd XV |
| Saturday, 18 December 2021 |
| Rochdale 2nd XV | Postponed | Leyland Warriors |
| Saturday, 8 January 2022 |
| Leyland Warriors | 5 | 5 | Preston Grasshoppers 3rd XV |
| Southport 2nd XV | 48 | 15 | Fylde Saracens (3rd XV) |
| Saturday, 15 January 2022 |
| Bolton 2nd XV | 19 | 32 | Southport 2nd XV |
| Chorley | 10 | 0 | Aspull 2nd XV |
| Leyland Warriors | 19 | 20 | Rochdale 2nd XV |
| Saturday, 22 January 2022 |
| Leigh 2nd XV | 19 | 19 | Leyland Warriors |
| Rochdale 2nd XV | 33 | 12 | Preston Grasshoppers 3rd XV |
| Southport 2nd XV | 17 | 18 | Chorley |
| Saturday, 29 January 2022 |
| Aspull 2nd XV | Home Walkover | Bolton 2nd XV |
| Preston Grasshoppers 3rd XV | 27 | 22 | Fylde Saracens (3rd XV) |
| Rochdale 2nd XV | 62 | 5 | Leigh 2nd XV |
| Saturday, 12 February 2022 |
| Aspull 2nd XV | 14 | 3 | Leyland Warriors |
| Bolton 2nd XV | 0 | 38 | Fylde Saracens (3rd XV) |
| Saturday, 19 February 2022 |
| Chorley | 5 | 0 | Fylde Saracens (3rd XV) |
| Preston Grasshoppers 3rd XV | 5 | 0 | Bolton 2nd XV |
| Rochdale 2nd XV | Home Walkover | Aspull 2nd XV |
| Saturday, 26 February 2022 |
| Leigh 2nd XV | 0 | 5 | Rochdale 2nd XV |
| Leyland Warriors | 5 | 0 | Southport 2nd XV |
| Saturday, 5 March 2022 |
| Aspull 2nd XV | 27 | 28 | Leigh 2nd XV |
| Bolton 2nd XV | 0 | 65 | Chorley |
| Southport 2nd XV | 14 | 31 | Rochdale 2nd XV |
| Saturday, 12 March 2022 |
| Leigh 2nd XV | 13 | 12 | Southport 2nd XV |
| Preston Grasshoppers 3rd XV | 50 | 17 | Chorley |
| Saturday, 19 March 2022 |
| Leigh 2nd XV | 24 | 17 | Fylde Saracens (3rd XV) |
| Leyland Warriors | 25 | 22 | Chorley |
| Saturday, 26 March 2022 |
| Aspull 2nd XV | 39 | 33 | Preston Grasshoppers 3rd XV |
| Fylde Saracens (3rd XV) | 46 | 0 | Leyland Warriors |
| Saturday, 2 April 2022 |
| Aspull 2nd XV | 0 | 49 | Southport 2nd XV |
| Leigh 2nd XV | 0 | 70 | Preston Grasshoppers 3rd XV |
| Leyland Warriors | Home Walkover | Bolton 2nd XV |
| Rochdale 2nd XV | 7 | 14 | Fylde Saracens (3rd XV) |
| Saturday, 9 April 2022 |
| Chorley | 12 | 22 | Leyland Warriors |
| Fylde Saracens (3rd XV) | 106 | 5 | Leigh 2nd XV |
| Rochdale 2nd XV | 69 | 0 | Bolton 2nd XV |
| Southport 2nd XV | 21 | 15 | Preston Grasshoppers 3rd XV |
| Saturday, 23 April 2022 |
| Chorley | 7 | 49 | Rochdale 2nd XV |
| Leigh 2nd XV | 43 | 19 | Bolton 2nd XV |
| Leyland Warriors | 7 | 5 | Fylde Saracens (3rd XV) |
| Saturday, 30 April 2022 |
| Chorley | 71 | 0 | Leigh 2nd XV |
| Fylde Saracens (3rd XV) | Home Walkover | Aspull 2nd XV |
| Rochdale 2nd XV | Home Walkover | Leyland Warriors |