| 1. Round | 18/07/2021 | Arsenal de Sarandí | - | San Lorenzo | 1:1 |  |
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| 2. Round | 24/07/2021 | San Lorenzo | - | Central Córdoba SdE | 1:0 | ||||
| 3. Round | 28/07/2021 | Boca Juniors | - | San Lorenzo | 0:2 |  |
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| 4. Round | 02/08/2021 | San Lorenzo | - | Banfield | 1:1 | |
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| 5. Round | 07/08/2021 | Unión de Santa Fe | - | San Lorenzo | 4:0 | ||||
| 6. Round | 16/08/2021 | Talleres de Córdoba | - | San Lorenzo | 2:0 |  |
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| 9. Round | 30/08/2021 | San Lorenzo | - | Patronato de Paraná | 3:0 | ||||
| 10. Round | 04/09/2021 | Platense | - | San Lorenzo | 1:1 | ||||
| 11. Round | 13/09/2021 | San Lorenzo | - | Racing Club | 1:1 | ||||
| 12. Round | 20/09/2021 | Rosario Central | - | San Lorenzo | 1:0 | |
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| 13. Round | 26/09/2021 | San Lorenzo | - | Defensa y Justicia | 2:1 | |
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| 15. Round | 11/10/2021 | San Lorenzo | - | Colón de Santa Fe | 1:2 | ||||
| 16. Round | 18/10/2021 | River Plate | - | San Lorenzo | 3:1 | |
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| 17. Round | 20/10/2021 | San Lorenzo | - | Lanús | 1:3 | ||||
| 18. Round | 24/10/2021 | Huracán | - | San Lorenzo | 2:1 | ||||
| 24. Round | 05/12/2021 | Independiente | - | San Lorenzo | 1:1 | |
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| 25. Round | 12/12/2021 | San Lorenzo | - | Newell's Old Boys | 3:2 |
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