| 1. Round | 03/06/2021 | Defensor Sporting | - | Rocha | 2:1 | ||||
| 3. Round | 16/06/2021 | Albion | - | Defensor Sporting | 2:2 | ||||
| 4. Round | 26/06/2021 | Defensor Sporting | - | Central Español | 4:0 | ||||
| 7. Round | 15/07/2021 | Villa Teresa | - | Defensor Sporting | 0:2 | ||||
| 8. Round | 22/07/2021 | Defensor Sporting | - | Juventud de Las Piedras | 1:2 |  |
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| 9. Round | 28/07/2021 | Uruguay Montevideo | - | Defensor Sporting | 0:2 | |
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| 10. Round | 05/08/2021 | Defensor Sporting | - | Rampla Juniors | 1:0 | ||||
| 11. Round | 14/08/2021 | Danubio | - | Defensor Sporting | 0:1 | ||||
| 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 | |
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| 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 | ||||
| 17. Round | 20/10/2021 | Racing | - | Defensor Sporting | 0:1 | ||||
| 18. Round | 29/10/2021 | Defensor Sporting | - | Villa Teresa | 1:2 | ||||
| 19. Round | 02/11/2021 | Juventud de Las Piedras | - | Defensor Sporting | 3:3 |
Uruguay