1st(1st leg) Crvena Zvezda - CFR Cluj 4:0 (2:0)
2nd (2nd leg) CFR Cluj - Crvena Zvezda 1:2 (1:1)
1st(1st leg): 17/08/2021 20:00 2nd (2nd leg): 26/08/2021 19:30 Winner: Crvena Zvezda
1st(1st leg) Celtic FC - AZ Alkmaar 2:0 (1:0)
2nd (2nd leg) AZ Alkmaar - Celtic FC 2:1 (2:1)
1st(1st leg): 18/08/2021 19:45 2nd (2nd leg): 26/08/2021 19:15 Winner: Celtic FC
1st(1st leg) Randers FC - Galatasaray 1:1 (0:1)
2nd (2nd leg) Galatasaray - Randers FC 2:1 (0:1)
1st(1st leg): 19/08/2021 18:00 2nd (2nd leg): 26/08/2021 19:00 Winner: Galatasaray
1st(1st leg) Omonia Nikosia - Royal Antwerp FC 4:2 (1:1)
2nd (2nd leg) Royal Antwerp FC - Omonia Nikosia 3:2 (1:0, 2:0, 2:0) pso
1st(1st leg): 19/08/2021 18:00 2nd (2nd leg): 26/08/2021 20:00 Winner: Royal Antwerp FC
1st(1st leg) Slavia Praha - Legia Warszawa 2:2 (2:2)
2nd (2nd leg) Legia Warszawa - Slavia Praha 2:1 (0:1)
1st(1st leg): 19/08/2021 18:00 2nd (2nd leg): 26/08/2021 20:00 Winner: Legia Warszawa
1st(1st leg) NŠ Mura - Sturm Graz 1:3 (1:1)
2nd (2nd leg) Sturm Graz - NŠ Mura 2:0 (1:0)
1st(1st leg): 19/08/2021 19:00 2nd (2nd leg): 26/08/2021 20:00 Winner: Sturm Graz
1st(1st leg) Fenerbahçe - HJK Helsinki 1:0 (0:0)
2nd (2nd leg) HJK Helsinki - Fenerbahçe 2:5 (1:2)
1st(1st leg): 19/08/2021 19:45 2nd (2nd leg): 26/08/2021 17:00 Winner: Fenerbahçe
1st(1st leg) Rapid Wien - Zorya Lugansk 3:0 (1:0)
2nd (2nd leg) Zorya Lugansk - Rapid Wien 2:3 (1:2)
1st(1st leg): 19/08/2021 20:00 2nd (2nd leg): 26/08/2021 17:30 Winner: Rapid Wien
1st(1st leg) Olympiakos Piräus - Slovan Bratislava 3:0 (1:0)
2nd (2nd leg) Slovan Bratislava - Olympiakos Piräus 2:2 (1:1)
1st(1st leg): 19/08/2021 20:00 2nd (2nd leg): 26/08/2021 19:45 Winner: Olympiakos Piräus
1st(1st leg) Rangers FC - FC Alashkert 1:0 (0:0)
2nd (2nd leg) FC Alashkert - Rangers FC 0:0 (0:0)
1st(1st leg): 19/08/2021 20:00 2nd (2nd leg): 26/08/2021 16:00 Winner: Rangers FC