| 3. Round | 31/07/2021 | Deportes Tolima | - | Alianza Petrolera | 1:1 | ||||
| 4. Round | 09/08/2021 | Atlético Junior | - | Deportes Tolima | 0:0 | ||||
| 5. Round | 14/08/2021 | Deportes Tolima | - | Deportivo Pasto | 1:0 |  |
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| 8. Round | 07/09/2021 | Deportes Tolima | - | Envigado FC | 2:0 | ||||
| 9. Round | 14/09/2021 | Atlético Huila | - | Deportes Tolima | 1:2 | ||||
| 10. Round | 19/09/2021 | Deportes Tolima | - | Deportivo Cali | 1:1 | ||||
| 13. Round | 09/10/2021 | Once Caldas | - | Deportes Tolima | 0:2 | ||||
| 14. Round | 16/10/2021 | Deportes Tolima | - | Atlético Huila | 1:0 | ||||
| 15. Round | 24/10/2021 | Independiente Medellín | - | Deportes Tolima | 2:2 |  |
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| 16. Round | 29/10/2021 | Deportes Tolima | - | América de Cali | 0:1 | ||||
| 17. Round | 03/11/2021 | Águilas Doradas | - | Deportes Tolima | 1:1 | ||||
| 18. Round | 07/11/2021 | Deportes Tolima | - | Millonarios | 3:2 | |
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| 19. Round | 15/11/2021 | Atlético Bucaramanga | - | Deportes Tolima | 1:1 | |
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Paraguay
Mexico