| 1. Round | 04/04/2021 | Cobreloa | - | Barnechea | 1:2 | ||||
| 2. Round | 18/04/2021 | San Marcos | - | Cobreloa | 0:0 | ||||
| 3. Round | 26/04/2021 | Cobreloa | - | Universidad de Concepción | 2:4 |  |
|||
| 4. Round | 03/05/2021 | Cobreloa | - | Coquimbo Unido | 1:1 | ||||
| 6. Round | 18/05/2021 | Cobreloa | - | Santiago Morning | 2:2 | |
|||
| 8. Round | 30/05/2021 | Cobreloa | - | San Luis | 1:0 | |
|||
| 10. Round | 09/07/2021 | Cobreloa | - | Deportes Iquique | 3:2 | ||||
| 11. Round | 14/07/2021 | Deportes Copiapó | - | Cobreloa | 0:0 | ||||
| 12. Round | 21/07/2021 | Cobreloa | - | Puerto Montt | 2:0 | |
|||
| 13. Round | 31/07/2021 | Deportes Temuco | - | Cobreloa | 1:0 | ||||
| 14. Round | 08/08/2021 | Cobreloa | - | Santa Cruz | 0:1 | ||||
| 17. Round | 29/08/2021 | Cobreloa | - | San Marcos | 0:3 dec. | ||||
| 18. Round | 02/09/2021 | Universidad de Concepción | - | Cobreloa | 0:0 | ||||
| 20. Round | 16/09/2021 | Cobreloa | - | Unión San Felipe | 2:1 |  |
|||
| 21. Round | 22/09/2021 | Santiago Morning | - | Cobreloa | 2:1 | ||||
| 22. Round | 26/09/2021 | Cobreloa | - | Fernández Vial | 1:2 | ||||
| 7. Round | 20/10/2021 | Fernández Vial | - | Cobreloa | 3:2 | ||||
| 29. Round | 06/11/2021 | Santa Cruz | - | Cobreloa | 2:2 | ||||
| 30. Round | 13/11/2021 | Cobreloa | - | Rangers | 4:1 | |
Argentina