| 14/8/21 | Boston United |  | 1-2 |  | Spennymoor | National League North | Jakemans Community Stadium | Watch |
| 21/8/21 | Spennymoor | | 3-2 |  | Southport | National League North | The Brewery Field | Watch |
| 28/8/21 | Leamington |  | 2-1 | | Spennymoor | National League North | Phillips 66 Community Stadium | Watch |
| 30/8/21 | Spennymoor | | 1-3 |  | York City | National League North | The Brewery Field | Watch |
| 4/9/21 | Hereford |  | 0-2 | | Spennymoor | National League North | Edgar Street | Watch |
| 11/9/21 | Spennymoor | | 6-0 |  | Farsley Celtic | National League North | The Brewery Field | Watch |
| 18/9/21 | AFC Fylde |  | 1-1 | | Spennymoor | Emirates FA Cup Second Round Qualifying | Mill Farm | Watch |
| 21/9/21 | Spennymoor | | 1-0 | | AFC Fylde | Emirates FA Cup Second Round Qualifying Replay | The Brewery Field | Watch |
| 25/9/21 | Kettering Town |  | 1-2 | | Spennymoor | National League North | Latimer Park | Watch |
| 2/10/21 | Spennymoor | | 0-0 | | Southport | Emirates FA Cup Third Round Qualifying | The Brewery Field | Watch |
| 5/10/21 | Southport | | 3-2 | | Spennymoor | Emirates FA Cup Third Round Qualifying Replay | The Pure Stadium | Watch |
| 9/10/21 | Spennymoor | | 1-0 |  | AFC Telford United | National League North | The Brewery Field | Watch |
| 23/10/21 | Spennymoor | | 2-2 |  | Curzon Ashton | National League North | The Brewery Field | Watch |
| 26/10/21 | AFC Fylde | | 2-0 | | Spennymoor | National League North | Mill Farm | Watch |
| 30/10/21 | Kidderminster Harriers |  | 4-0 | | Spennymoor | National League North | Aggborough | Watch |
| 6/11/21 | Spennymoor | | 0-2 |  | Alfreton Town | National League North | The Brewery Field | Watch |
| 9/11/21 | Brackley |  | 2-0 | | Spennymoor | National League North | St James Park | Watch |
| 13/11/21 | Bradford (Park Avenue) |  | 1-1 | | Spennymoor | National League North | Horsfall Stadium | Watch |
| 20/11/21 | Spennymoor | | 1-2 |  | Gateshead | National League North | The Brewery Field | Watch |
| 30/11/21 | Spennymoor | | 0-0 (3-1 on pens) |  | Chorley | FA Trophy Second Round | The Brewery Field | Watch |
| 4/12/21 | Gloucester |  | 2-0 | | Spennymoor | National League North | New Meadow Park | |
| 11/12/21 | Spennymoor | | 4-2 |  | Chester | National League North | The Brewery Field | Watch |
| 18/12/21 | Radcliffe FC |  | 0-1 | | Spennymoor | Buildbase FA Trophy Third Round | Neuven Stadium | |
| 22/12/21 | Gateshead | | 0-5 | | Spennymoor | Durham Challenge Cup First Round | Gateshead International Stadium | |
| 26/12/21 | Spennymoor | | 1-1 |  | Darlington | National League North | The Brewery Field | Watch |
| 28/12/21 | Blyth Spartans |  | 3-1 | | Spennymoor | National League North | Croft Park | |
| 1/1/22 | Darlington | | 1-1 | | Spennymoor | National League North | Blackwell Meadows | |
| 8/1/22 | Spennymoor | | 2-1 |  | Guiseley | National League North | The Brewery Field | Watch |
| 15/1/22 | Spennymoor | | 3-1 |  | Plymouth Parkway FC | Buildbase FA Trophy Fourth Round | The Brewery Field | Watch |
| 18/1/22 | Spennymoor | | 3-0 |  | Whickham FC | Durham Challenge Cup Second Round | The Brewery Field | |
| 22/1/22 | Spennymoor | | 1-1 | | Boston United | National League North | The Brewery Field | Watch |
| 29/1/22 | Alfreton Town | | 3-2 | | Spennymoor | National League North | The Impact Arena | Watch |
| 12/2/22 | Dagenham & Redbridge |  | 2-0 | | Spennymoor | Buildbase FA Trophy Fifth Round | Chigwell Construction Stadium | Watch |
| 19/2/22 | Gateshead | | 2-1 | | Spennymoor | National League North | International Stadium | Watch |
| 22/2/22 | Chester | | 0-2 | | Spennymoor | National League North | Swansway Chester Stadium | Watch |
| 23/02/22 | Spennymoor |  | 1-4 |  | Ryhope CW | Durham Challenge Cup | The Brewery Field | |
| 26/2/22 | Spennymoor | | 0-0 | | Gloucester | National League North | The Brewery Field | Watch |
| 5/3/22 | Farsley Celtic | | 1-2 | | Spennymoor | National League North | The Citadel | Watch |
| 8/3/22 | Chorley | | 0-2 | | Spennymoor | National League North | Victory Park | Watch |
| 12/3/22 | Spennymoor | | 2-1 | | Kettering Town | National League North | The Brewery Field | Watch |
| 15/3/22 | Spennymoor | | 0-0 | | Kidderminster Harriers | National League North | The Brewery Field | Watch |
| 19/3/22 | AFC Telford United | | 2-0 | | Spennymoor | National League North | New Bucks Head | Watch |
| 22/3/22 | Spennymoor | | 0-1 | | AFC Fylde | National League North | The Brewery Field | Watch |
| 26/3/22 | Spennymoor | | 1-1 | | Brackley Town | National League North | The Brewery Field | Watch |
| 2/4/22 | Curzon Ashton | | 0-3 | | Spennymoor | National League North | Tameside Stadium | Watch |
| 5/4/22 | Spennymoor | | 0-2 | | Bradford (Park Avenue) | National League North | The Brewery Field | Watch |
| 9/4/22 | Spennymoor | | 1-0 | | Leamington | National League North | The Brewery Field | Watch |
| 15/4/22 | York City | | 1-0 | | Spennymoor | National League North | York Community Stadium | Watch |
| 18/4/22 | Spennymoor | | 3-0 | | Blyth Spartans | National League North | The Brewery Field | Watch |
| 23/4/22 | Southport | | 1-1 | | Spennymoor | National League North | The Pure Stadium | Watch |
| 30/4/22 | Spennymoor | | 1-0 | | Hereford | National League North | The Brewery Field | Watch |
| 2/5/22 | Guiseley | | 1-0 | | Spennymoor | National League North | Nethermoor Park | |
| 7/5/22 | Spennymoor | | 2-0 | | Chorley | National League North | The Brewery Field | |
