Club Guaraní 0-5 Atlético Nacional *
| 19.03.2021 | Atlético Nacional | 3-0 | Club Guaraní | |
| 12.03.2021 | Club Guaraní | 0-2 | Atlético Nacional | |
*Grêmio/RS 8-2 Ayacucho FC
| 17.03.2021 | Ayacucho FC | 1-2 | Grêmio/RS | |
| 11.03.2021 | Grêmio/RS | 6-1 | Ayacucho FC | |
Univ Católica Quito 2-3 Club Libertad *
| 17.03.2021 | Club Libertad | 2-2 | Univ Católica Quito | |
| 10.03.2021 | Univ Católica Quito | 0-1 | Club Libertad | |
*Santos/SP 3-2 Deportivo Lara
| 16.03.2021 | Deportivo Lara | 1-1 | Santos/SP | |
| 09.03.2021 | Santos/SP | 2-1 | Deportivo Lara | |
Caracas FC 2-5 Junior Barranquilla *
| 18.03.2021 | Junior Barranquilla | 3-1 | Caracas FC | |
| 11.03.2021 | Caracas FC | 1-2 | Junior Barranquilla | |
Mvo Wanderers 1-5 Bolívar *
| 16.03.2021 | Bolívar | 5-0 | Mvo Wanderers | |
| 09.03.2021 | Mvo Wanderers | 1-0 | Bolívar | |
Unión Española 3-6 Independiente del Valle *
| 17.03.2021 | Independiente del Valle | 6-2 | Unión Española | |
| 10.03.2021 | Unión Española | 1-0 | Independiente del Valle | |
Univ de Chile 1-3 San Lorenzo *
| 18.03.2021 | San Lorenzo | 2-0 | Univ de Chile | |
| 11.03.2021 | Univ de Chile | 1-1 | San Lorenzo | |