| 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 | ||||
| 5. Round | 10/05/2021 | Unión San Felipe | - | Cobreloa | 0:0 | ||||
| 6. Round | 18/05/2021 | Cobreloa | - | Santiago Morning | 2:2 | ||||
| 9. Round | 07/06/2021 | CD Magallanes | - | Cobreloa | 2:2 |  |
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| 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 |  |
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| 22. Round | 26/09/2021 | Cobreloa | - | Fernández Vial | 1:2 | ||||
| 23. Round | 02/10/2021 | San Luis | - | Cobreloa | 1:0 | |
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| 24. Round | 06/10/2021 | Cobreloa | - | CD Magallanes | 2:1 | ||||
| 25. Round | 13/10/2021 | Deportes Iquique | - | Cobreloa | 1:0 | ||||
| 7. Round | 20/10/2021 | Fernández Vial | - | Cobreloa | 3:2 | ||||
| 27. Round | 28/10/2021 | Puerto Montt | - | Cobreloa | 0:0 |
Uruguay