| 17. Round | 28/08/2021 | Rangers | - | San Luis | 0:1 |  |
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| 18. Round | 01/09/2021 | San Luis | - | Puerto Montt | 0:1 | ||||
| 19. Round | 07/09/2021 | Unión San Felipe | - | San Luis | 1:1 | ||||
| 20. Round | 16/09/2021 | San Luis | - | Deportes Iquique | 1:1 |  |
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| 21. Round | 22/09/2021 | Fernández Vial | - | San Luis | 2:2 | |
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| 22. Round | 26/09/2021 | Deportes Copiapó | - | San Luis | 4:1 | ||||
| 25. Round | 12/10/2021 | San Luis | - | Santa Cruz | 0:0 | ||||
| 26. Round | 20/10/2021 | San Luis | - | Santiago Morning | 2:2 | ||||
| 27. Round | 25/10/2021 | Universidad de Concepción | - | San Luis | 0:2 | ||||
| 28. Round | 31/10/2021 | San Luis | - | Coquimbo Unido | 0:0 | ||||
| 29. Round | 06/11/2021 | CD Magallanes | - | San Luis | 3:3 | |
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| 30. Round | 12/11/2021 | San Luis | - | Barnechea | 2:1 | |
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