| 1. Round | 12/09/2021 | Plaza Colonia | - | Peñarol | 1:2 |  |
|||
| 2. Round | 19/09/2021 | Montevideo City Torque | - | Plaza Colonia | 2:2 | ||||
| 3. Round | 24/09/2021 | Plaza Colonia | - | Villa Española | 4:0 | |
|||
| 4. Round | 03/10/2021 | Nacional | - | Plaza Colonia | 2:1 | |
|||
| 5. Round | 11/10/2021 | Plaza Colonia | - | Cerrito | 3:3 | |
 |
||
| 6. Round | 16/10/2021 | Liverpool | - | Plaza Colonia | 0:1 | ||||
| 7. Round | 20/10/2021 | Plaza Colonia | - | River Plate | 0:0 | |
|||
| 8. Round | 25/10/2021 | Cerro Largo | - | Plaza Colonia | 1:0 | ||||
| 9. Round | 30/10/2021 | Plaza Colonia | - | Progreso | 2:1 | ||||
| 10. Round | 04/11/2021 | Sud América | - | Plaza Colonia | 1:1 | |
|||
| 11. Round | 09/11/2021 | Plaza Colonia | - | Deportivo Maldonado | 1:0 |  |
|||
| 13. Round | 22/11/2021 | Boston River | - | Plaza Colonia | 2:0 | ||||
| 14. Round | 26/11/2021 | Plaza Colonia | - | Montevideo Wanderers | 0:1 | ||||
| 15. Round | 04/12/2021 | Rentistas | - | Plaza Colonia | 2:3 |
Uruguay