| 1. Round | 17/07/2021 | Independiente Medellín | - | Águilas Doradas | 1:1 | ||||
| 2. Round | 26/07/2021 | Deportivo Cali | - | Independiente Medellín | 0:0 | ||||
| 5. Round | 14/08/2021 | Independiente Medellín | - | América de Cali | 2:0 | ||||
| 6. Round | 22/08/2021 | Millonarios | - | Independiente Medellín | 2:0 |  |
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| 9. Round | 11/09/2021 | Jaguares de Córdoba | - | Independiente Medellín | 0:1 | ||||
| 11. Round | 27/09/2021 | Deportes Quindío | - | Independiente Medellín | 1:0 | ||||
| 14. Round | 17/10/2021 | Atlético Nacional | - | Independiente Medellín | 1:1 | ||||
| 15. Round | 24/10/2021 | Independiente Medellín | - | Deportes Tolima | 2:2 | ||||
| 16. Round | 27/10/2021 | Alianza Petrolera | - | Independiente Medellín | 3:0 | ||||
| 18. Round | 07/11/2021 | Patriotas FC | - | Independiente Medellín | 0:1 | ||||
| 19. Round | 14/11/2021 | Independiente Medellín | - | Atlético Nacional | 0:0 | ||||
| 20. Round | 21/11/2021 | Deportivo Pasto | - | Independiente Medellín | 1:1 |
Colombia