| 5. Round | 27/04/2021 | Audax Italiano | - | Deportes Melipilla | 1:0 | ||||
| 6. Round | 02/05/2021 | Deportes Melipilla | - | Universidad Católica | 2:0 | ||||
| 7. Round | 08/05/2021 | Santiago Wanderers | - | Deportes Melipilla | 0:3 | ||||
| 8. Round | 23/05/2021 | Deportes Melipilla | - | Antofagasta | 1:1 | ||||
| 9. Round | 29/05/2021 | La Serena | - | Deportes Melipilla | 5:1 | ||||
| 27. Round | 20/10/2021 | O'Higgins | - | Deportes Melipilla | 1:2 | ||||
| 28. Round | 24/10/2021 | Deportes Melipilla | - | Universidad de Chile | 3:0 | ||||
| 29. Round | 31/10/2021 | Unión La Calera | - | Deportes Melipilla | 2:3 | ||||
| 30. Round | 03/11/2021 | Deportes Melipilla | - | Cobresal | 2:1 |  |
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| 33. Round | 27/11/2021 | Deportes Melipilla | - | Everton | 1:0 | ||||
| 34. Round | 05/12/2021 | Huachipato | - | Deportes Melipilla | 3:1 | |
Chile