| 2. Round | 25/07/2021 | Guaireña FC | - | River Plate | 1:2 | ||||
| 3. Round | 31/07/2021 | River Plate | - | Cerro Porteño | 0:0 | ||||
| 4. Round | 09/08/2021 | Sol de América | - | River Plate | 1:0 | ||||
| 6. Round | 22/08/2021 | 12 de Octubre de Itauguá | - | River Plate | 2:2 | ||||
| 7. Round | 30/08/2021 | River Plate | - | Guaraní | 1:5 | ||||
| 8. Round | 11/09/2021 | Sportivo Luqueño | - | River Plate | 0:2 | ||||
| 9. Round | 18/09/2021 | River Plate | - | Libertad | 0:1 | ||||
| 11. Round | 03/10/2021 | River Plate | - | Guaireña FC | 1:1 | ||||
| 14. Round | 29/10/2021 | Club Nacional | - | River Plate | 1:1 |
Uruguay