| 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 | | 19:45 | | Chorley | FA Trophy Second Round | The Brewery Field | |
| 4/12/21 | Gloucester | | 15:00 | | Spennymoor | National League North | New Meadow Park | |
| 11/12/21 | Spennymoor | | 15:00 | | Chester | National League North | The Brewery Field | |
| 26/12/21 | Spennymoor | | 15:00 | | Darlington | National League North | The Brewery Field | |
| 28/12/21 | Blyth Spartans | | 15:00 | | Spennymoor | National League North | Croft Park | |
| 1/1/22 | Darlington | | 15:00 | | Spennymoor | National League North | Blackwell Meadows | |
| 8/1/22 | Spennymoor | | 15:00 | | Guiseley | National League North | The Brewery Field | |
| 15/1/22 | Chorley | | 15:00 | | Spennymoor | National League North | Victory Park | |
| 22/1/22 | Spennymoor | | 15:00 | | Boston United | National League North | The Brewery Field | |
| 29/1/22 | Alfreton Town | | 15:00 | | Spennymoor | National League North | The Impact Arena | |
| 5/2/22 | Spennymoor | | 15:00 | | Kidderminster | National League North | The Brewery Field | |
| 12/2/22 | Spennymoor | | 15:00 | | Bradford (Park Avenue) | National League North | The Brewery Field | |
| 19/2/22 | Gateshead | | 15:00 | | Spennymoor | National League North | International Stadium | |
| 22/2/22 | Chester | | 19:45 | | Spennymoor | National League North | Swansway Chester Stadium | |
| 26/2/22 | Spennymoor | | 15:00 | | Gloucester | National League North | The Brewery Field | |
| 5/3/22 | Farsley Celtic | | 15:00 | | Spennymoor | National League North | The Citadel | |
| 12/3/22 | Spennymoor | | 15:00 | | Kettering Town | National League North | The Brewery Field | |
| 19/3/22 | AFC Telford United | | 15:00 | | Spennymoor | National League North | New Bucks Head | |
| 22/3/22 | Spennymoor | | 19:45 | | AFC Fylde | National League North | The Brewery Field | |
| 26/3/22 | Spennymoor | | 15:00 | | Brackley Town | National League North | The Brewery Field | |
| 2/4/22 | Curzon Ashton | | 15:00 | | Spennymoor | National League North | Tameside Stadium | |
| 9/4/22 | Spennymoor | | 15:00 | | Leamington | National League North | The Brewery Field | |
| 15/4/22 | York City | | 15:00 | | Spennymoor | National League North | York Community Stadium | |
| 18/4/22 | Spennymoor | | 15:00 | | Blyth Spartans | National League North | The Brewery Field | |
| 23/4/22 | Southport | | 15:00 | | Spennymoor | National League North | The Pure Stadium | |
| 30/4/22 | Spennymoor | | 15:00 | | Hereford | National League North | The Brewery Field | |
| 2/5/22 | Guiseley | | 15:00 | | Spennymoor | National League North | Nethermoor Park | |
| 7/5/22 | Spennymoor | | 15:00 | | Chorley | National League North | The Brewery Field | |
