| 12. Round | 16/09/2021 | Rocha | - | Defensor Sporting | 1:2 | ||||
| 13. Round | 23/09/2021 | Defensor Sporting | - | CA Cerro | 2:0 | ||||
| 14. Round | 30/09/2021 | Defensor Sporting | - | Albion | 0:1 | ||||
| 15. Round | 05/10/2021 | Central Español | - | Defensor Sporting | 1:0 | ||||
| 16. Round | 12/10/2021 | Defensor Sporting | - | Atenas | 1:1 |  |
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| 19. Round | 02/11/2021 | Juventud de Las Piedras | - | Defensor Sporting | 3:3 |
Uruguay