| 4. Round | 24/11/2021 | AO Kavala | - | Xanthi FC | 0:6 |  |
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| 6. Round | 05/12/2021 | Niki Volou FC | - | Xanthi FC | 0:1 | ||||
| 7. Round | 11/12/2021 | Xanthi FC | - | Olympiakos Volou | 2:0 | ||||
| 8. Round | 15/12/2021 | PAOK Saloniki II | - | Xanthi FC | 0:1 |  |
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| 9. Round | 19/12/2021 | Xanthi FC | - | AO Trikala | 5:0 | ||||
| 10. Round | 29/12/2021 | AE Lárissa | - | Xanthi FC | 4:0 | ||||
| 11. Round | 26/01/2022 | Xanthi FC | - | Apollon Lárissa | 0:0 | ||||
| 16. Round | 30/01/2022 | Apollon Pontou | - | Xanthi FC | 0:0 | ||||
| 17. Round | 06/02/2022 | Xanthi FC | - | Anagennisi Karditsa | 5:2 | ||||
| 22. Round | 06/03/2022 | Almopos Arideas | - | Xanthi FC | 2:2 | ||||
| 23. Round | 09/03/2022 | Xanthi FC | - | Niki Volou FC | 0:0 | ||||
| 28. Round | 03/04/2022 | Apollon Lárissa | - | Xanthi FC | 0:0 | ||||
| 29. Round | 06/04/2022 | Xanthi FC | - | Olympiakos Piraeus II | 2:1 | ||||
| 31. Round | 13/04/2022 | Xanthi FC | - | AEP Iraklis FC | 3:3 | ||||
| 32. Round | 17/04/2022 | Veria FC | - | Xanthi FC | 0:0 | ||||
| 33. Round | 27/04/2022 | Xanthi FC | - | Apollon Pontou | 2:1 | |
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| 34. Round | 01/05/2022 | Anagennisi Karditsa | - | Xanthi FC | 4:0 |
Greece