| 3. Round | 25/04/2021 | Deportes Iquique | - | San Marcos | 1:2 | ||||
| 8. Round | 01/06/2021 | San Marcos | - | Unión San Felipe | 3:1 | ||||
| 9. Round | 07/06/2021 | San Luis | - | San Marcos | 0:1 |  |
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| 12. Round | 25/07/2021 | San Marcos | - | Barnechea | 0:3 dec. | |
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| 13. Round | 03/08/2021 | Universidad de Concepción | - | San Marcos | 3:1 | ||||
| 14. Round | 08/08/2021 | San Marcos | - | Rangers | 1:0 | ||||
| 15. Round | 15/08/2021 | Santa Cruz | - | San Marcos | 2:0 | ||||
| 16. Round | 22/08/2021 | San Marcos | - | CD Magallanes | 1:2 | ||||
| 4. Round | 27/08/2021 | San Marcos | - | Fernández Vial | 2:1 | ||||
| 17. Round | 29/08/2021 | Cobreloa | - | San Marcos | 0:3 dec. | |
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| 18. Round | 02/09/2021 | San Marcos | - | Deportes Iquique | 4:2 | ||||
| 19. Round | 07/09/2021 | Fernández Vial | - | San Marcos | 1:2 | |
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| 20. Round | 16/09/2021 | San Marcos | - | Santiago Morning | 4:0 | |
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| 21. Round | 22/09/2021 | Deportes Temuco | - | San Marcos | 2:0 | ||||
| 25. Round | 12/10/2021 | Deportes Copiapó | - | San Marcos | 1:1 |
Chile