| 1. Round | 03/06/2021 | Defensor Sporting | - | Rocha | 2:1 | ||||
| 2. Round | 10/06/2021 | CA Cerro | - | Defensor Sporting | 0:0 | ||||
| 3. Round | 16/06/2021 | Albion | - | Defensor Sporting | 2:2 | ||||
| 4. Round | 26/06/2021 | Defensor Sporting | - | Central Español | 4:0 | ||||
| 5. Round | 01/07/2021 | Atenas | - | Defensor Sporting | 2:0 |  |
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| 6. Round | 09/07/2021 | Defensor Sporting | - | Racing | 1:4 | ||||
| 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 | |
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| 18. Round | 29/10/2021 | Defensor Sporting | - | Villa Teresa | 1:2 | |
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| 21. Round | 18/11/2021 | Rampla Juniors | - | Defensor Sporting | 0:5 |
Uruguay