| 1. Round | 07/02/2022 | River Plate | - | Montevideo Wanderers | 1:1 |  |
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| 2. Round | 12/02/2022 | Plaza Colonia | - | River Plate | 0:1 | ||||
| 3. Round | 19/02/2022 | River Plate | - | Boston River | 1:2 | ||||
| 4. Round | 28/02/2022 | River Plate | - | Cerrito | 3:1 | |
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| 5. Round | 05/03/2022 | River Plate | - | Cerro Largo | 1:1 | ||||
| 6. Round | 20/03/2022 | River Plate | - | Fénix | 3:1 | |
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| 7. Round | 03/04/2022 | Defensor Sporting | - | River Plate | 3:2 |  |
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| 8. Round | 10/04/2022 | River Plate | - | Albion | 4:1 | |
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| 9. Round | 17/04/2022 | Nacional | - | River Plate | 1:1 | ||||
| 10. Round | 23/04/2022 | River Plate | - | Danubio | 0:0 | ||||
| 11. Round | 07/05/2022 | Deportivo Maldonado | - | River Plate | 2:1 | ||||
| 12. Round | 13/05/2022 | River Plate | - | Rentistas | 1:0 |
Uruguay