| 4. Round | 26/02/2022 | Montevideo Wanderers | - | Defensor Sporting | 1:0 | ||||
| 5. Round | 12/03/2022 | Defensor Sporting | - | Plaza Colonia | 0:0 | ||||
| 6. Round | 21/03/2022 | Boston River | - | Defensor Sporting | 1:1 |  |
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| 7. Round | 03/04/2022 | Defensor Sporting | - | River Plate | 3:2 | |
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| 8. Round | 08/04/2022 | Cerro Largo | - | Defensor Sporting | 0:0 | ||||
| 9. Round | 16/04/2022 | Defensor Sporting | - | Fénix | 2:1 | ||||
| 10. Round | 26/04/2022 | Defensor Sporting | - | Cerrito | 0:0 | ||||
| 11. Round | 07/05/2022 | Albion | - | Defensor Sporting | 0:3 | |
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| 12. Round | 14/05/2022 | Defensor Sporting | - | Nacional | 0:2 | ||||
| 13. Round | 22/05/2022 | Danubio | - | Defensor Sporting | 1:2 | |
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| 15. Round | 05/06/2022 | Rentistas | - | Defensor Sporting | 1:0 |
Uruguay