1st(1st leg) Niki Volou FC - Panetolikos 0:1 (0:1)
2nd (2nd leg) Panetolikos - Niki Volou FC 1:0 (0:0)
1st(1st leg): 01/12/2021 13:00 2nd (2nd leg): 22/12/2021 15:00 Winner: Panetolikos
1st(1st leg) Aris Saloniki - OFI Heraklion 3:1 (2:0)
2nd (2nd leg) OFI Heraklion - Aris Saloniki 0:2 (0:0)
1st(1st leg): 01/12/2021 15:00 2nd (2nd leg): 23/12/2021 13:00 Winner: Aris Saloniki
1st(1st leg) Levadiakos - Olympiakos Piraeus 3:2 (2:1)
2nd (2nd leg) Olympiakos Piraeus - Levadiakos 2:0 (2:0)
1st(1st leg): 01/12/2021 15:00 2nd (2nd leg): 22/12/2021 17:00 Winner: Olympiakos Piraeus
1st(1st leg) Panathinaikos - Volos NFC 2:1 (1:0)
2nd (2nd leg) Volos NFC - Panathinaikos 0:0 (0:0)
1st(1st leg): 01/12/2021 17:00 2nd (2nd leg): 23/12/2021 15:00 Winner: Panathinaikos
1st(1st leg) AEK Athen - AE Kifisias 4:0 (0:0)
2nd (2nd leg) AE Kifisias - AEK Athen 1:1 (0:0)
1st(1st leg): 01/12/2021 18:15 2nd (2nd leg): 23/12/2021 17:00 Winner: AEK Athen
1st(1st leg) AE Lárissa - PAOK Saloniki 1:1 (0:0)
2nd (2nd leg) PAOK Saloniki - AE Lárissa 3:1 (1:0)
1st(1st leg): 01/12/2021 19:30 2nd (2nd leg): 22/12/2021 15:00 Winner: PAOK Saloniki
1st(1st leg) Agios Nikolaos - Anagennisi Karditsa 0:1 (0:0)
2nd (2nd leg) Anagennisi Karditsa - Agios Nikolaos 5:0 (1:0)
1st(1st leg): 02/12/2021 13:00 2nd (2nd leg): 22/12/2021 13:00 Winner: Anagennisi Karditsa
1st(1st leg) Lamia - Ionikos Nikea 2:0 (1:0)
2nd (2nd leg) Ionikos Nikea - Lamia 0:1 (0:1)
1st(1st leg): 02/12/2021 15:00 2nd (2nd leg): 23/12/2021 15:00 Winner: Lamia