| 1. Round | 03/06/2021 | Defensor Sporting | - | Rocha | 2:1 | ||||
| 2. Round | 10/06/2021 | CA Cerro | - | Defensor Sporting | 0:0 | ||||
| 5. Round | 01/07/2021 | Atenas | - | Defensor Sporting | 2:0 | ||||
| 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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| 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 |  |
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| 20. Round | 10/11/2021 | Defensor Sporting | - | Uruguay Montevideo | 2:0 | ||||
| 21. Round | 18/11/2021 | Rampla Juniors | - | Defensor Sporting | 0:5 | |
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| 22. Round | 24/11/2021 | Defensor Sporting | - | Danubio | 0:1 |
Uruguay