| 1. Round | 15/08/2021 | FC Schalke 04 II | - | 1. FC Köln II | 1:2 | ||||
| 2. Round | 21/08/2021 | Alemannia Aachen | - | FC Schalke 04 II | 1:1 | ||||
| 3. Round | 25/08/2021 | FC Schalke 04 II | - | Bor. Mönchengladbach II | 1:0 | ||||
| 4. Round | 28/08/2021 | Sportfreunde Lotte | - | FC Schalke 04 II | 2:0 | ||||
| 5. Round | 04/09/2021 | FC Schalke 04 II | - | FC Wegberg-Beeck | 2:0 |  |
|||
| 6. Round | 10/09/2021 | SV Rödinghausen | - | FC Schalke 04 II | 1:0 | ||||
| 7. Round | 14/09/2021 | FC Schalke 04 II | - | Rot Weiss Ahlen | 5:3 | ||||
| 8. Round | 17/09/2021 | Rot-Weiss Essen | - | FC Schalke 04 II | 1:0 | |
|||
| 11. Round | 12/10/2021 | FC Schalke 04 II | - | Fortuna Köln | 1:1 | |
|||
| 12. Round | 15/10/2021 | Fortuna Düsseldorf II | - | FC Schalke 04 II | 5:1 | ||||
| 13. Round | 23/10/2021 | FC Schalke 04 II | - | VfB Homberg | 0:0 | ||||
| 14. Round | 29/10/2021 | Preußen Münster | - | FC Schalke 04 II | 3:0 | ||||
| 15. Round | 07/11/2021 | Bonner SC | - | FC Schalke 04 II | 4:3 | ||||
| 18. Round | 26/11/2021 | FC Schalke 04 II | - | KFC Uerdingen 05 | 4:1 | ||||
| 19. Round | 04/12/2021 | SC Wiedenbrück | - | FC Schalke 04 II | 2:2 |
Germany