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| 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 Piraeus | - | Slovan Bratislava | 3:0 (1:0) | ||
| 2nd (2nd leg) | Slovan Bratislava | - | Olympiakos Piraeus | 2:2 (1:1) | ||
| 1st(1st leg): 19/08/2021 20:00 | 2nd (2nd leg): 26/08/2021 19:45 | Winner: Olympiakos Piraeus | ||||
| 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 | ||||
