| 1. Round | 03/06/2021 | Defensor Sporting | - | Rocha | 2:1 | ||||
| 6. Round | 09/07/2021 | Defensor Sporting | - | Racing | 1:4 | ||||
| 7. Round | 15/07/2021 | Villa Teresa | - | Defensor Sporting | 0:2 |  |
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| 8. Round | 22/07/2021 | Defensor Sporting | - | Juventud de Las Piedras | 1:2 | ||||
| 9. Round | 28/07/2021 | Uruguay Montevideo | - | Defensor Sporting | 0:2 | |
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| 12. Round | 16/09/2021 | Rocha | - | Defensor Sporting | 1:2 | ||||
| 15. Round | 05/10/2021 | Central Español | - | Defensor Sporting | 1:0 | |
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| 16. Round | 12/10/2021 | Defensor Sporting | - | Atenas | 1:1 | ||||
| 20. Round | 10/11/2021 | Defensor Sporting | - | Uruguay Montevideo | 2:0 | ||||
| 21. Round | 18/11/2021 | Rampla Juniors | - | Defensor Sporting | 0:5 | ||||
| 22. Round | 24/11/2021 | Defensor Sporting | - | Danubio | 0:1 |
Uruguay