| 1. Round | 17/03/2021 | Atlético Porteño | - | Atlético Santo Domingo | 1:1 |  |
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| 3. Round | 01/04/2021 | Cumbayá | - | Atlético Santo Domingo | 2:1 | ||||
| 4. Round | 06/04/2021 | Atlético Santo Domingo | - | Independiente Juniors | 1:1 |  |
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| 5. Round | 14/04/2021 | Chacaritas FC | - | Atlético Santo Domingo | 1:0 | ||||
| 6. Round | 21/04/2021 | Atlético Santo Domingo | - | Gualaceo SC | 1:0 | |
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| 7. Round | 05/05/2021 | Guayaquil SC | - | Atlético Santo Domingo | 0:1 | ||||
| 8. Round | 13/05/2021 | El Nacional | - | Atlético Santo Domingo | 1:0 | ||||
| 9. Round | 20/05/2021 | Atlético Santo Domingo | - | Liga de Portoviejo | 3:2 | ||||
| 14. Round | 13/06/2021 | Gualaceo SC | - | Atlético Santo Domingo | 3:0 | ||||
| 15. Round | 16/06/2021 | Atlético Santo Domingo | - | Guayaquil SC | 0:1 | ||||
| 16. Round | 20/06/2021 | Atlético Santo Domingo | - | El Nacional | 0:2 | ||||
| 17. Round | 23/06/2021 | Liga de Portoviejo | - | Atlético Santo Domingo | 2:0 | ||||
| 18. Round | 27/06/2021 | Atlético Santo Domingo | - | Atlético Porteño | 2:1 | ||||
| 19. Round | 03/07/2021 | Atlético Santo Domingo | - | Gualaceo SC | 1:4 | ||||
| 20. Round | 08/07/2021 | Chacaritas FC | - | Atlético Santo Domingo | 2:1 | |
Ecuador