| 1. Jornada | 18.07.2021 | Club Olimpia | - | River Plate | 1:3 |  |
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| 2. Jornada | 25.07.2021 | Guaireña FC | - | River Plate | 1:2 | ||||
| 3. Jornada | 31.07.2021 | River Plate | - | Cerro Porteño | 0:0 | ||||
| 5. Jornada | 14.08.2021 | River Plate | - | Club Nacional | 1:0 | ||||
| 6. Jornada | 22.08.2021 | 12 de Octubre de Itauguá | - | River Plate | 2:2 |  |
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| 7. Jornada | 30.08.2021 | River Plate | - | Guaraní | 1:5 | |
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| 8. Jornada | 12.09.2021 | Sportivo Luqueño | - | River Plate | 0:2 | ||||
| 9. Jornada | 18.09.2021 | River Plate | - | Libertad | 0:1 | ||||
| 10. Jornada | 27.09.2021 | River Plate | - | Club Olimpia | 1:2 | ||||
| 12. Jornada | 19.10.2021 | Cerro Porteño | - | River Plate | 2:0 | ||||
| 16. Jornada | 20.11.2021 | Guaraní | - | River Plate | 2:1 | ||||
| 17. Jornada | 26.11.2021 | River Plate | - | Sportivo Luqueño | 0:0 | ||||
| 18. Jornada | 03.12.2021 | Libertad | - | River Plate | 5:0 |
Paraguay