| 2. Round | 19/09/2021 | Apollon Smyrnis | - | Volos NFC | 1:3 |  |
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| 3. Round | 22/09/2021 | Olympiakos Piraeus | - | Apollon Smyrnis | 4:1 | ||||
| 4. Round | 27/09/2021 | Apollon Smyrnis | - | Ionikos Nikea | 0:0 | |
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| 5. Round | 02/10/2021 | Aris Saloniki | - | Apollon Smyrnis | 0:0 | ||||
| 6. Round | 16/10/2021 | Apollon Smyrnis | - | Asteras Tripolis | 0:1 | ||||
| 7. Round | 23/10/2021 | Apollon Smyrnis | - | PAS Giannina | 1:0 | ||||
| 8. Round | 30/10/2021 | PAOK Saloniki | - | Apollon Smyrnis | 4:1 | |
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| 9. Round | 06/11/2021 | Apollon Smyrnis | - | AEK Athen | 2:2 | |
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| 10. Round | 21/11/2021 | Panetolikos | - | Apollon Smyrnis | 1:0 |  |
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| 12. Round | 04/12/2021 | Atromitos | - | Apollon Smyrnis | 4:1 | ||||
| 16. Round | 05/01/2022 | Apollon Smyrnis | - | Olympiakos Piraeus | 0:0 | ||||
| 18. Round | 15/01/2022 | Apollon Smyrnis | - | Aris Saloniki | 0:0 | |
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| 21. Round | 02/02/2022 | Apollon Smyrnis | - | PAOK Saloniki | 0:2 | ||||
| 23. Round | 12/02/2022 | Apollon Smyrnis | - | Panetolikos | 0:0 | |
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| 14. Round | 16/02/2022 | Apollon Smyrnis | - | Panathinaikos | 0:3 | |
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| 26. Round | 06/03/2022 | OFI Heraklion | - | Apollon Smyrnis | 2:0 |
Greece