| 1. Round | 04/04/2021 | CD Magallanes | - | San Marcos | 1:3 | ||||
| 2. Round | 18/04/2021 | San Marcos | - | Cobreloa | 0:0 | ||||
| 3. Round | 25/04/2021 | Deportes Iquique | - | San Marcos | 1:2 | ||||
| 6. Round | 18/05/2021 | San Marcos | - | Deportes Temuco | 1:2 | ||||
| 7. Round | 24/05/2021 | Coquimbo Unido | - | San Marcos | 1:0 | ||||
| 9. Round | 07/06/2021 | San Luis | - | San Marcos | 0:1 | ||||
| 10. Round | 09/07/2021 | San Marcos | - | Deportes Copiapó | 0:1 | ||||
| 11. Round | 15/07/2021 | Puerto Montt | - | San Marcos | 2:2 | ||||
| 4. Round | 27/08/2021 | San Marcos | - | Fernández Vial | 2:1 | ||||
| 17. Round | 29/08/2021 | Cobreloa | - | San Marcos | 0:3 dec. | ||||
| 18. Round | 02/09/2021 | San Marcos | - | Deportes Iquique | 4:2 |  |
|||
| 19. Round | 07/09/2021 | Fernández Vial | - | San Marcos | 1:2 | ||||
| 20. Round | 16/09/2021 | San Marcos | - | Santiago Morning | 4:0 | ||||
| 21. Round | 22/09/2021 | Deportes Temuco | - | San Marcos | 2:0 | ||||
| 25. Round | 12/10/2021 | Deportes Copiapó | - | San Marcos | 1:1 | ||||
| 26. Round | 22/10/2021 | San Marcos | - | Puerto Montt | 1:2 | ||||
| 27. Round | 27/10/2021 | Barnechea | - | San Marcos | 1:1 | ||||
| 28. Round | 31/10/2021 | San Marcos | - | Universidad de Concepción | 0:0 | ||||
| 29. Round | 06/11/2021 | Rangers | - | San Marcos | 1:1 |
Chile