| 1. Round | 16/05/2021 | Cerrito | - | River Plate | 3:1 |  |
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| 2. Round | 24/05/2021 | River Plate | - | Liverpool | 3:2 |  |
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| 3. Round | 30/05/2021 | Deportivo Maldonado | - | River Plate | 0:0 | ||||
| 4. Round | 06/06/2021 | Cerro Largo | - | River Plate | 2:4 | ||||
| 5. Round | 12/06/2021 | River Plate | - | Progreso | 4:0 | ||||
| 6. Round | 19/06/2021 | Sud América | - | River Plate | 1:2 | ||||
| 7. Round | 22/06/2021 | River Plate | - | Plaza Colonia | 0:1 | ||||
| 8. Round | 26/06/2021 | Fénix | - | River Plate | 3:4 | |
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| 9. Round | 03/07/2021 | River Plate | - | Boston River | 1:1 | ||||
| 10. Round | 10/07/2021 | Montevideo Wanderers | - | River Plate | 1:2 | |
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| 11. Round | 17/07/2021 | River Plate | - | Rentistas | 0:0 | ||||
| 12. Round | 01/08/2021 | Peñarol | - | River Plate | 2:0 | ||||
| 13. Round | 07/08/2021 | River Plate | - | Montevideo City Torque | 3:3 | ||||
| 14. Round | 15/08/2021 | Villa Española | - | River Plate | 1:1 | ||||
| 15. Round | 21/08/2021 | River Plate | - | Nacional | 2:0 |
Uruguay