| 2. Jornada | 11.06.2021 | CA Cerro | - | Defensor Sporting | 0:0 | ||||
| 3. Jornada | 16.06.2021 | Albion | - | Defensor Sporting | 2:2 |  |
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| 4. Jornada | 26.06.2021 | Defensor Sporting | - | Central Español | 4:0 | ||||
| 5. Jornada | 01.07.2021 | Atenas | - | Defensor Sporting | 2:0 | ||||
| 6. Jornada | 09.07.2021 | Defensor Sporting | - | Racing | 1:4 | ||||
| 8. Jornada | 22.07.2021 | Defensor Sporting | - | Juventud de Las Piedras | 1:2 | ||||
| 9. Jornada | 28.07.2021 | Uruguay Montevideo | - | Defensor Sporting | 0:2 | ||||
| 16. Jornada | 12.10.2021 | Defensor Sporting | - | Atenas | 1:1 | |
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| 17. Jornada | 20.10.2021 | Racing | - | Defensor Sporting | 0:1 | |
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| 19. Jornada | 02.11.2021 | Juventud de Las Piedras | - | Defensor Sporting | 3:3 | ||||
| 20. Jornada | 10.11.2021 | Defensor Sporting | - | Uruguay Montevideo | 2:0 | ||||
| 21. Jornada | 18.11.2021 | Rampla Juniors | - | Defensor Sporting | 0:5 |  |
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| 22. Jornada | 24.11.2021 | Defensor Sporting | - | Danubio | 0:1 |
Uruguay