| 1. Round | 17/01/2021 | Atlético Junior | - | Independiente Medellín | 1:0 | ||||
| 2. Round | 23/01/2021 | Independiente Medellín | - | Patriotas FC | 2:1 | ||||
| 3. Round | 01/02/2021 | Atlético Bucaramanga | - | Independiente Medellín | 0:1 | ||||
| 5. Round | 07/02/2021 | Deportes Tolima | - | Independiente Medellín | 2:1 | ||||
| 7. Round | 17/02/2021 | Independiente Medellín | - | Boyacá Chicó | 1:0 |  |
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| 8. Round | 21/02/2021 | Santa Fe | - | Independiente Medellín | 0:0 | |
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| 9. Round | 26/02/2021 | Independiente Medellín | - | Deportivo Cali | 1:1 | ||||
| 10. Round | 28/02/2021 | Envigado FC | - | Independiente Medellín | 1:1 | ||||
| 11. Round | 05/03/2021 | Independiente Medellín | - | La Equidad | 1:1 | ||||
| 12. Round | 14/03/2021 | Águilas Doradas | - | Independiente Medellín | 0:2 | ||||
| 15. Round | 28/03/2021 | Independiente Medellín | - | Atlético Nacional | 0:0 | ||||
| 17. Round | 07/04/2021 | Deportivo Pereira | - | Independiente Medellín | 1:0 | ||||
| 19. Round | 18/04/2021 | Once Caldas | - | Independiente Medellín | 2:0 | |
Colombia