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| 1st(1st leg) | San Lorenzo | - | Santos FC | 1:3 (0:2) | ||
| 2nd (2nd leg) | Santos FC | - | San Lorenzo | 2:2 (1:0) | ||
| 1st(1st leg): 07/04/2021 01:30 | 2nd (2nd leg): 14/04/2021 01:30 | Winner: Santos FC | ||||
| 1st(1st leg) | Libertad | - | Atlético Nacional | 1:0 (0:0) | ||
| 2nd (2nd leg) | Atlético Nacional | - | Libertad | 4:1 (1:1) | ||
| 1st(1st leg): 08/04/2021 01:30 | 2nd (2nd leg): 15/04/2021 01:30 | Winner: Atlético Nacional | ||||
| 1st(1st leg) | Bolívar | - | Atlético Junior | 2:1 (1:1) | ||
| 2nd (2nd leg) | Atlético Junior | - | Bolívar | 3:0 (1:0) | ||
| 1st(1st leg): 09/04/2021 01:30 | 2nd (2nd leg): 16/04/2021 01:30 | Winner: Atlético Junior | ||||
| 1st(1st leg) | Independiente del Valle | - | Grêmio Porto Alegre | 2:1 (0:1) | ||
| 2nd (2nd leg) | Grêmio Porto Alegre | - | Independiente del Valle | 1:2 (1:1) | ||
| 1st(1st leg): 09/04/2021 23:15 | 2nd (2nd leg): 14/04/2021 23:15 | Winner: Independiente del Valle | ||||
