| 3. Round | 08/08/2021 | Barcelona | - | Guayaquil City | 2:1 | ||||
| 6. Round | 29/08/2021 | Guayaquil City | - | Técnico Universitario | 1:0 | ||||
| 7. Round | 18/09/2021 | Orense SC | - | Guayaquil City | 2:0 | ||||
| 8. Round | 25/09/2021 | Guayaquil City | - | 9 de Octubre | 0:1 | ||||
| 9. Round | 03/10/2021 | LDU Quito | - | Guayaquil City | 3:1 |  |
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| 10. Round | 16/10/2021 | Guayaquil City | - | Olmedo | 4:2 |  |
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| 11. Round | 24/10/2021 | Manta | - | Guayaquil City | 1:1 | |
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| 12. Round | 31/10/2021 | Guayaquil City | - | Emelec | 0:1 | ||||
| 13. Round | 08/11/2021 | Guayaquil City | - | Independiente del Valle | 0:2 | ||||
| 14. Round | 21/11/2021 | Mushuc Runa | - | Guayaquil City | 1:0 | ||||
| 15. Round | 28/11/2021 | Guayaquil City | - | Aucas | 1:0 |
Paraguay