| 3. Round | 01/04/2021 | Cumbayá | - | Atlético Santo Domingo | 2:1 | ||||
| 4. Round | 06/04/2021 | Atlético Santo Domingo | - | Independiente Juniors | 1:1 | ||||
| 6. Round | 21/04/2021 | Atlético Santo Domingo | - | Gualaceo SC | 1:0 |  |
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| 9. Round | 20/05/2021 | Atlético Santo Domingo | - | Liga de Portoviejo | 3:2 | ||||
| 10. Round | 27/05/2021 | América de Quito | - | Atlético Santo Domingo | 1:1 | |
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| 13. Round | 09/06/2021 | Atlético Santo Domingo | - | Chacaritas FC | 3:0 | ||||
| 14. Round | 13/06/2021 | Gualaceo SC | - | Atlético Santo Domingo | 3:0 | |
Ecuador