| 5. Round | 26/09/2021 | FCE Rheine | - | Holzwickeder SC | 3:0 | ||||
| 6. Round | 03/10/2021 | Holzwickeder SC | - | TSG Sprockhövel | 0:5 | ||||
| 7. Round | 10/10/2021 | Hammer SpVg | - | Holzwickeder SC | 1:1 | ||||
| 8. Round | 17/10/2021 | Holzwickeder SC | - | Sportfreunde Siegen | 0:2 | ||||
| 9. Round | 24/10/2021 | SpVgg Vreden | - | Holzwickeder SC | 1:0 | ||||
| 10. Round | 31/10/2021 | Holzwickeder SC | - | FC Gütersloh | 1:3 | ||||
| 14. Round | 25/11/2021 | Holzwickeder SC | - | SC Paderborn 07 II | 0:6 | ||||
| 15. Round | 05/12/2021 | RSV Meinerzhagen | - | Holzwickeder SC | 4:1 | ||||
| 16. Round | 12/12/2021 | Holzwickeder SC | - | Westfalia Herne | 1:1 |
Germany