| 1. Round | 12/09/2021 | Boston River | - | Montevideo Wanderers | 1:3 | ||||
| 2. Round | 17/09/2021 | Rentistas | - | Boston River | 1:2 |  |
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| 3. Round | 26/09/2021 | Boston River | - | Peñarol | 2:5 | ||||
| 4. Round | 03/10/2021 | Montevideo City Torque | - | Boston River | 4:3 |  |
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| 5. Round | 10/10/2021 | Boston River | - | Villa Española | 1:0 | |
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| 7. Round | 21/10/2021 | Boston River | - | Cerrito | 3:2 | |
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| 8. Round | 24/10/2021 | Liverpool | - | Boston River | 2:2 | ||||
| 12. Round | 14/11/2021 | Sud América | - | Boston River | 1:2 | |
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| 14. Round | 30/11/2021 | Fénix | - | Boston River | 0:0 | |
Uruguay