| 4. Round | 09/08/2021 | Sol de América | - | River Plate | 1:0 | ||||
| 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 | ||||
| 10. Round | 26/09/2021 | River Plate | - | Club Olimpia | 1:2 | ||||
| 11. Round | 03/10/2021 | River Plate | - | Guaireña FC | 1:1 | ||||
| 12. Round | 19/10/2021 | Cerro Porteño | - | River Plate | 2:0 | ||||
| 15. Round | 05/11/2021 | River Plate | - | 12 de Octubre de Itauguá | 0:2 |
Paraguay