| 2021-07-31 15:00:0031/07/21 | Guisborough Town v Bishop Auckland | 0 - 1 | Division 1 | 2021-22 | King George V Ground | | 363 |
| Christopher Winn (82) |
| 2021-08-04 19:45:0004/08/21 | Guisborough Town v Sunderland RCA | 2 - 0 | Division 1 | 2021-22 | King George V Ground | | 300 |
| Louis Johnson 2 (34 pen, 65) |
| 2021-08-07 15:00:0007/08/21 | Penrith v Guisborough Town | 1 - 2 | | 2021-22 | The Frenchfield Stadium | FA CupExtra Preliminary Round | |
| 2021-08-11 19:45:0011/08/21 | Guisborough Town v Ashington | 0 - 2 | Division 1 | 2021-22 | King George V Ground | | 271 |
| Dean Briggs (11) Paul Robinson (48), Briggs missed pen (70) |
| 2021-08-14 15:00:0014/08/21 | Guisborough Town v Seaham Red Star | 2 - 0 | Division 1 | 2021-22 | King George V Ground | | 170 |
| Steven Roberts (19) Brad Plant (90) |
| 2021-08-21 15:00:3021/08/21 | North Shields v Guisborough Town | 2 - 0 | | 2021-22 | Daren Persson Stadium | FA CupPreliminary Round | 275 |
| Callum Smith (31) Cameron Cunningham (59) |
| 2021-08-25 19:45:0025/08/21 | Guisborough Town v West Allotment Celtic | 3 - 0 | Division 1 | 2021-22 | King George V Ground | | 241 |
| Brad Plant 2 (3, 84) Steven Roberts (41) |
| 2021-08-28 15:00:0028/08/21 | Guisborough Town v Newton Aycliffe | 0 - 0 | Division 1 | 2021-22 | King George V Ground | | 241 |
| Harry Ord sent off (10), Steven Roberts sent off (88) |
| Sonni Coleman missed penalty (11) |
| 2021-08-30 11:00:0030/08/21 | Northallerton Town v Guisborough Town | 2 - 2 | Division 1 | 2021-22 | The Calvert Stadium | | 206 |
| Lewis Rees (36) Andrew Shepherd (44) |
| Callum Martin (34) Harry Ord (83) |
| 2021-09-04 15:00:0004/09/21 | Billingham Town v Guisborough Town | 0 - 0 | Division 1 | 2021-22 | Bedford Terrace | | 170 |
| 2021-09-11 15:00:0011/09/21 | Carlisle City v Guisborough Town | 1 - 0 | | 2021-22 | Gillford Park Stadium | FA VaseFirst Round Qualifying | 146 |
| Jordan Holt (64) |
| Robert Dean sent off (45) |
| 2021-09-18 15:00:0018/09/21 | Guisborough Town v Thornaby | 0 - 4 | Division 1 | 2021-22 | King George V Ground | | 316 |
| Elliott Beddow 2 (22 pen, 53) Craig Hutchinson (31) Lee Moore (90) |
| 2021-09-25 15:00:0025/09/21 | Crook Town v Guisborough Town | 1 - 3 | Division 1 | 2021-22 | The Sir Tom Cowie Millfield | | 265 |
| Mason Hurworth (47) |
| Steven Roberts 3 (13 pen, 63 pen, 82), Louis Johnson missed pen (6) |
| 2021-10-02 15:00:0002/10/21 | Consett v Guisborough Town | 3 - 0 | Division 1 | 2021-22 | Belle View Stadium | | 455 |
| Jake Orrell (4) Colin Larkin (27) Luke Carr (68 pen) |
| 2021-10-05 19:30:0005/10/21 | Whickham v Guisborough Town [POSTPONED] | 19:30:007:30 pm | Division 1 | 2021-22 | Glebe Sports Ground | | |
| 2021-10-09 15:00:0009/10/21 | Guisborough Town v West Auckland Town | 0 - 1 | Division 1 | 2021-22 | King George V Ground | | 349 |
| Joseph Bartliff sent off (57) |
| Jordan Blinco (29) |
| 2021-10-16 15:00:0016/10/21 | Sunderland Ryhope C.W. v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Ryhope Recreation Ground | | |
| 2021-10-20 19:30:0020/10/21 | Newcastle Benfield v Guisborough Town | 19:30:007:30 pm | Division 1 | 2021-22 | Sam Smith's Park | | |
| 2021-10-23 15:00:0023/10/21 | Whitley Bay v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Hillheads Park | | |
| 2021-10-30 15:00:0030/10/21 | Guisborough Town v North Shields | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2021-11-06 15:00:0006/11/21 | Redcar Athletic v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Green Lane | | |
| 2021-11-13 15:00:0013/11/21 | Guisborough Town v Penrith | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2021-11-20 15:00:0020/11/21 | Sunderland RCA v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Sunderland LGV Park | | |
| 2021-11-27 15:00:0027/11/21 | Ashington v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | The dwmedia Stadium | | |
| 2021-12-11 15:00:0011/12/21 | West Allotment Celtic v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | East Palmersville Sports Pavilion | | |
| 2021-12-18 15:00:0018/12/21 | Guisborough Town v Whickham | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2021-12-27 11:00:0027/12/21 | Guisborough Town v Northallerton Town | 11:00:0011:00 am | Division 1 | 2021-22 | King George V Ground | | |
| 2022-01-08 15:00:0008/01/22 | Bishop Auckland v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Voneus Stadium | | |
| 2022-01-15 15:00:0015/01/22 | Guisborough Town v Newcastle Benfield | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2022-01-22 15:00:0022/01/22 | Seaham Red Star v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | The Ferguson Motor Repairs Stadium | | |
| 2022-01-29 15:00:0029/01/22 | Guisborough Town v Crook Town | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2022-02-05 15:00:0005/02/22 | Newton Aycliffe v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | The Beaumont Landscapes Stadium | | |
| 2022-02-12 15:00:0012/02/22 | Guisborough Town v Billingham Town | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2022-02-19 15:00:0019/02/22 | Thornaby v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Teesdale Park | | |
| 2022-02-26 15:00:0026/02/22 | Guisborough Town v Consett | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2022-03-05 15:00:0005/03/22 | Penrith v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | The Frenchfield Stadium | | |
| 2022-03-12 15:00:0012/03/22 | West Auckland Town v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Wanted Stadium | | |
| 2022-03-19 15:00:0019/03/22 | Guisborough Town v Sunderland Ryhope C.W. | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2022-03-26 15:00:0026/03/22 | Guisborough Town v Whitley Bay | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
| 2022-04-02 15:00:0002/04/22 | North Shields v Guisborough Town | 15:00:003:00 pm | Division 1 | 2021-22 | Daren Persson Stadium | | |
| 2022-04-09 15:00:0009/04/22 | Guisborough Town v Redcar Athletic | 15:00:003:00 pm | Division 1 | 2021-22 | King George V Ground | | |
