| 1. Round | 11/09/2021 | Cerro Largo | - | Nacional | 0:3 dec. | ||||
| 3. Round | 25/09/2021 | Sud América | - | Nacional | 0:2 | ||||
| 4. Round | 03/10/2021 | Nacional | - | Plaza Colonia | 2:1 | ||||
| 5. Round | 10/10/2021 | Fénix | - | Nacional | 1:2 |  |
 |
||
| 6. Round | 16/10/2021 | Nacional | - | Boston River | 3:2 | ||||
| 7. Round | 22/10/2021 | Montevideo Wanderers | - | Nacional | 1:0 | ||||
| 9. Round | 31/10/2021 | Peñarol | - | Nacional | 0:0 | ||||
| 10. Round | 04/11/2021 | Nacional | - | Montevideo City Torque | 2:0 | ||||
| 11. Round | 07/11/2021 | Villa Española | - | Nacional | 1:2 | ||||
| 12. Round | 13/11/2021 | Deportivo Maldonado | - | Nacional | 1:0 | ||||
| 14. Round | 26/11/2021 | Liverpool | - | Nacional | 2:2 | ||||
| 15. Round | 04/12/2021 | Nacional | - | River Plate | 4:2 |
Uruguay