| 11. Round | 15/07/2021 | Rangers | - | Santa Cruz | 1:3 | ||||
| 14. Round | 08/08/2021 | Cobreloa | - | Santa Cruz | 0:1 | ||||
| 15. Round | 15/08/2021 | Santa Cruz | - | San Marcos | 2:0 | ||||
| 19. Round | 05/09/2021 | Puerto Montt | - | Santa Cruz | 2:2 | ||||
| 23. Round | 03/10/2021 | Deportes Iquique | - | Santa Cruz | 6:1 |  |
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| 25. Round | 12/10/2021 | San Luis | - | Santa Cruz | 0:0 | ||||
| 26. Round | 19/10/2021 | Santa Cruz | - | Rangers | 1:0 | ||||
| 27. Round | 23/10/2021 | CD Magallanes | - | Santa Cruz | 1:1 |
Chile