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| 1st(1st leg) | Young Buffaloes | - | AS Vita Club | 2:2 (1:0) | ||
| 2nd (2nd leg) | AS Vita Club | - | Young Buffaloes | 4:1 (1:0) | ||
| 1st(1st leg): 22/12/2020 13:00 | 2nd (2nd leg): 06/01/2021 14:30 | Winner: AS Vita Club | ||||
| 1st(1st leg) | Jwaneng Galaxy | - | Mamelodi Sundowns | 0:2 (0:1) | ||
| 2nd (2nd leg) | Mamelodi Sundowns | - | Jwaneng Galaxy | 3:1 (1:0) | ||
| 1st(1st leg): 22/12/2020 13:30 | 2nd (2nd leg): 05/01/2021 14:30 | Winner: Mamelodi Sundowns | ||||
| 1st(1st leg) | Teungueth FC | - | Raja Casablanca | 0:0 (0:0) | ||
| 2nd (2nd leg) | Raja Casablanca | - | Teungueth FC | 1:3 (0:0, 0:0) pso | ||
| 1st(1st leg): 22/12/2020 17:00 | 2nd (2nd leg): 05/01/2021 18:00 | Winner: Teungueth FC | ||||
| 1st(1st leg) | Gazelle FC | - | Zamalek | dnp | ||
| 2nd (2nd leg) | Zamalek | - | Gazelle FC | dnp | ||
| 1st(1st leg): 23/12/2020 | 2nd (2nd leg): 06/01/2021 | Winner: Gazelle FC | ||||
| 1st(1st leg) | Al Merrikh SC | - | Enyimba Aba | 3:0 (2:0) | ||
| 2nd (2nd leg) | Enyimba Aba | - | Al Merrikh SC | 2:1 (1:1) | ||
| 1st(1st leg): 23/12/2020 13:00 | 2nd (2nd leg): 06/01/2021 14:30 | Winner: Al Merrikh SC | ||||
| 1st(1st leg) | Nkana FC | - | Petro Atlético | 1:1 (0:0) | ||
| 2nd (2nd leg) | Petro Atlético | - | Nkana FC | 1:0 (0:0) | ||
| 1st(1st leg): 23/12/2020 13:00 | 2nd (2nd leg): 06/01/2021 16:00 | Winner: Petro Atlético | ||||
| 1st(1st leg) | FC Platinum | - | Simba SC | 1:0 (1:0) | ||
| 2nd (2nd leg) | Simba SC | - | FC Platinum | 4:0 (1:0) | ||
| 1st(1st leg): 23/12/2020 13:00 | 2nd (2nd leg): 06/01/2021 14:00 | Winner: Simba SC | ||||
| 1st(1st leg) | AS SONIDEP | - | Al Ahly SC | 0:1 (0:1) | ||
| 2nd (2nd leg) | Al Ahly SC | - | AS SONIDEP | 4:0 (2:0) | ||
| 1st(1st leg): 23/12/2020 14:00 | 2nd (2nd leg): 05/01/2021 17:00 | Winner: Al Ahly SC | ||||
| 1st(1st leg) | AS Bouenguidi | - | TP Mazembe | 1:2 (1:1) | ||
| 2nd (2nd leg) | TP Mazembe | - | AS Bouenguidi | 2:1 (2:0) | ||
| 1st(1st leg): 23/12/2020 14:30 | 2nd (2nd leg): 06/01/2021 13:30 | Winner: TP Mazembe | ||||
| 1st(1st leg) | Asante Kotoko | - | Al Hilal Omdurman | 0:1 (0:0) | ||
| 2nd (2nd leg) | Al Hilal Omdurman | - | Asante Kotoko | 2:0 dec. | ||
| 1st(1st leg): 23/12/2020 15:00 | 2nd (2nd leg): 06/01/2021 13:00 | Winner: Al Hilal Omdurman | ||||
| 1st(1st leg) | Stade Malien | - | Wydad AC | 1:0 (0:0) | ||
| 2nd (2nd leg) | Wydad AC | - | Stade Malien | 3:0 (1:0) | ||
| 1st(1st leg): 23/12/2020 16:00 | 2nd (2nd leg): 06/01/2021 16:00 | Winner: Wydad AC | ||||
| 1st(1st leg) | RC Abidjan | - | Horoya AC | 1:1 (0:1) | ||
| 2nd (2nd leg) | Horoya AC | - | RC Abidjan | 1:0 (0:0) | ||
| 1st(1st leg): 23/12/2020 16:00 | 2nd (2nd leg): 06/01/2021 16:00 | Winner: Horoya AC | ||||
| 1st(1st leg) | Al Ahly Benghazi | - | Espérance de Tunis | 0:0 (0:0) | ||
| 2nd (2nd leg) | Espérance de Tunis | - | Al Ahly Benghazi | 3:2 (1:0) | ||
| 1st(1st leg): 23/12/2020 16:00 | 2nd (2nd leg): 06/01/2021 14:00 | Winner: Espérance de Tunis | ||||
| 1st(1st leg) | Kaizer Chiefs | - | CD 1º de Agosto | 0:0 (0:0) | ||
| 2nd (2nd leg) | CD 1º de Agosto | - | Kaizer Chiefs | 0:1 (0:1) | ||
| 1st(1st leg): 23/12/2020 16:00 | 2nd (2nd leg): 05/01/2021 15:00 | Winner: Kaizer Chiefs | ||||
| 1st(1st leg) | CR Bélouizdad | - | Gor Mahia FC | 6:0 (4:0) | ||
| 2nd (2nd leg) | Gor Mahia FC | - | CR Bélouizdad | 1:2 (1:0) | ||
| 1st(1st leg): 26/12/2020 19:45 | 2nd (2nd leg): 06/01/2021 12:00 | Winner: CR Bélouizdad | ||||
| 1st(1st leg) | MC Alger | - | CS Sfaxien | 2:0 (2:0) | ||
| 2nd (2nd leg) | CS Sfaxien | - | MC Alger | 1:0 (1:0) | ||
| 1st(1st leg): 28/12/2020 19:45 | 2nd (2nd leg): 06/01/2021 14:00 | Winner: MC Alger | ||||
