| 1. Round | 01/09/2021 | Cortuluá | - | Real Santander | 2:0 | ||||
| 8. Round | 11/09/2021 | Real Santander | - | Barranquilla FC | 1:1 | ||||
| 9. Round | 18/09/2021 | Bogotá FC | - | Real Santander | 1:1 | ||||
| 10. Round | 24/09/2021 | Real Santander | - | Atlético FC | 0:2 | ||||
| 11. Round | 02/10/2021 | Orsomarso SC | - | Real Santander | 3:1 |  |
Colombia