| 1. Round | 07/08/2010 | FC 08 Homburg | - | FC Schalke 04 II | 1:2 |  |
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| 2. Round | 21/08/2010 | FC Schalke 04 II | - | SV 07 Elversberg | 0:0 |  |
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| 3. Round | 27/08/2010 | Bor. Mönchengladbach II | - | FC Schalke 04 II | 0:1 | |
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| 4. Round | 08/09/2010 | FC Schalke 04 II | - | 1. FC Köln II | 1:0 | ||||
| 5. Round | 11/09/2010 | SC Verl | - | FC Schalke 04 II | 4:1 | ||||
| 6. Round | 18/09/2010 | FC Schalke 04 II | - | 1. FC Kaiserslautern II | 1:0 | |
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| 7. Round | 21/09/2010 | Wuppertaler SV | - | FC Schalke 04 II | 2:4 | |
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| 8. Round | 25/09/2010 | FC Schalke 04 II | - | Preußen Münster | 1:1 | ||||
| 9. Round | 01/10/2010 | Eintracht Trier | - | FC Schalke 04 II | 1:0 | ||||
| 10. Round | 17/10/2010 | FC Schalke 04 II | - | Arminia Bielefeld II | 1:1 | ||||
| 11. Round | 23/10/2010 | Borussia Dortmund II | - | FC Schalke 04 II | 2:0 | |
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| 12. Round | 30/10/2010 | FC Schalke 04 II | - | 1. FSV Mainz 05 II | 0:2 | ||||
| 13. Round | 05/11/2010 | Sportfreunde Lotte | - | FC Schalke 04 II | 1:0 |
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