| 23. Round | 23/01/2021 | FC Schalke 04 II | - | Rot-Weiß Oberhausen | 0:1 | ||||
| 25. Round | 06/02/2021 | SV Rödinghausen | - | FC Schalke 04 II | 2:1 | ||||
| 27. Round | 20/02/2021 | SV 19 Straelen | - | FC Schalke 04 II | 2:0 | ||||
| 24. Round | 23/02/2021 | FC Schalke 04 II | - | FC Wegberg-Beeck | 0:0 | ||||
| 22. Round | 10/03/2021 | Bor. Mönchengladbach II | - | FC Schalke 04 II | 0:1 | ||||
| 30. Round | 13/03/2021 | FC Schalke 04 II | - | Alemannia Aachen | 2:2 | ||||
| 31. Round | 20/03/2021 | 1. FC Köln II | - | FC Schalke 04 II | 5:2 | ||||
| 26. Round | 24/03/2021 | FC Schalke 04 II | - | SV Bergisch Gladbach 09 | 0:2 | ||||
| 33. Round | 03/04/2021 | Rot-Weiss Essen | - | FC Schalke 04 II | 5:0 | ||||
| 34. Round | 07/04/2021 | FC Schalke 04 II | - | SC Wiedenbrück | 2:1 | ||||
| 35. Round | 10/04/2021 | Bonner SC | - | FC Schalke 04 II | 0:3 | ||||
| 37. Round | 24/04/2021 | Borussia Dortmund II | - | FC Schalke 04 II | 3:3 |  |
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| 38. Round | 08/05/2021 | FC Schalke 04 II | - | Rot Weiss Ahlen | 6:1 | ||||
| 39. Round | 15/05/2021 | SV Lippstadt 08 | - | FC Schalke 04 II | 2:0 |  |
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| 40. Round | 22/05/2021 | FC Schalke 04 II | - | Fortuna Düsseldorf II | 2:0 | ||||
| 41. Round | 29/05/2021 | Fortuna Köln | - | FC Schalke 04 II | 4:1 |
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