| 1. Round | 11/09/2021 | Panetolikos | - | Asteras Tripolis | 0:0 | ||||
| 2. Round | 19/09/2021 | Atromitos | - | Panetolikos | 1:2 | ||||
| 3. Round | 22/09/2021 | Panetolikos | - | PAOK Saloniki | 1:2 | ||||
| 4. Round | 26/09/2021 | Lamia | - | Panetolikos | 2:2 | ||||
| 6. Round | 17/10/2021 | Panetolikos | - | OFI Heraklion | 1:2 | ||||
| 7. Round | 24/10/2021 | Aris Saloniki | - | Panetolikos | 5:1 | ||||
| 8. Round | 30/10/2021 | Panetolikos | - | Olympiakos Piraeus | 1:2 | ||||
| 9. Round | 06/11/2021 | PAS Giannina | - | Panetolikos | 3:0 | ||||
| 11. Round | 28/11/2021 | Panathinaikos | - | Panetolikos | 2:0 |  |
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| 12. Round | 04/12/2021 | Volos NFC | - | Panetolikos | 1:2 | ||||
| 13. Round | 11/12/2021 | Panetolikos | - | Ionikos Nikea | 2:2 | ||||
| 14. Round | 14/12/2021 | Asteras Tripolis | - | Panetolikos | 1:0 | ||||
| 15. Round | 18/12/2021 | Panetolikos | - | Atromitos | 2:1 | ||||
| 16. Round | 12/01/2022 | PAOK Saloniki | - | Panetolikos | 2:0 | ||||
| 18. Round | 16/01/2022 | AEK Athen | - | Panetolikos | 1:2 | ||||
| 19. Round | 22/01/2022 | OFI Heraklion | - | Panetolikos | 2:4 | ||||
| 20. Round | 30/01/2022 | Panetolikos | - | Aris Saloniki | 0:2 | ||||
| 21. Round | 02/02/2022 | Olympiakos Piraeus | - | Panetolikos | 3:1 | ||||
| 17. Round | 16/02/2022 | Panetolikos | - | Lamia | 1:0 |
Greece