| 2. Round | 25/07/2021 | Atlético Nacional | - | Deportes Tolima | 1:0 | ||||
| 3. Round | 31/07/2021 | Deportes Tolima | - | Alianza Petrolera | 1:1 |  |
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| 4. Round | 09/08/2021 | Atlético Junior | - | Deportes Tolima | 0:0 | ||||
| 5. Round | 14/08/2021 | Deportes Tolima | - | Deportivo Pasto | 1:0 | ||||
| 6. Round | 22/08/2021 | La Equidad | - | Deportes Tolima | 1:1 | ||||
| 7. Round | 30/08/2021 | Jaguares de Córdoba | - | Deportes Tolima | 0:3 | ||||
| 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 |  |
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| 11. Round | 26/09/2021 | Patriotas FC | - | Deportes Tolima | 0:0 | ||||
| 12. Round | 02/10/2021 | Deportes Tolima | - | Santa Fe | 0:0 | ||||
| 13. Round | 09/10/2021 | Once Caldas | - | Deportes Tolima | 0:2 | |
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| 14. Round | 16/10/2021 | Deportes Tolima | - | Atlético Huila | 1:0 | |
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| 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 | ||||
| 20. Round | 21/11/2021 | Deportes Tolima | - | Deportes Quindío | 3:1 |
Colombia