| 1. Round | 05/02/2022 | Defensor Sporting | - | Liverpool | 0:3 |  |
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| 2. Round | 13/02/2022 | Peñarol | - | Defensor Sporting | 0:1 | |
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| 3. Round | 19/02/2022 | Defensor Sporting | - | Montevideo City Torque | 1:3 | ||||
| 5. Round | 12/03/2022 | Defensor Sporting | - | Plaza Colonia | 0:0 | ||||
| 7. Round | 03/04/2022 | Defensor Sporting | - | River Plate | 3:2 | ||||
| 8. Round | 08/04/2022 | Cerro Largo | - | Defensor Sporting | 0:0 | |
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| 9. Round | 16/04/2022 | Defensor Sporting | - | Fénix | 2:1 | ||||
| 11. Round | 07/05/2022 | Albion | - | Defensor Sporting | 0:3 | ||||
| 13. Round | 22/05/2022 | Danubio | - | Defensor Sporting | 1:2 | ||||
| 14. Round | 29/05/2022 | Defensor Sporting | - | Deportivo Maldonado | 1:1 | ||||
| 15. Round | 05/06/2022 | Rentistas | - | Defensor Sporting | 1:0 |
Uruguay