| 1. Round | 29/07/2021 | TM Fútbol Club | - | Leones Negros | 3:2 | ||||
| 2. Round | 04/08/2021 | Mineros de Zacatecas | - | Leones Negros | 2:1 | ||||
| 3. Round | 13/08/2021 | Leones Negros | - | Dorados de Sinaloa | 0:0 | ||||
| 6. Round | 05/09/2021 | Atlante | - | Leones Negros | 2:0 | ||||
| 8. Round | 15/09/2021 | Leones Negros | - | Tapatío | 3:0 | ||||
| 9. Round | 22/09/2021 | Cancún FC | - | Leones Negros | 0:1 | ||||
| 10. Round | 01/10/2021 | Leones Negros | - | Atlético Morelia | 2:1 |  |
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| 11. Round | 07/10/2021 | Pumas Tabasco | - | Leones Negros | 1:1 | |
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| 12. Round | 14/10/2021 | Leones Negros | - | Club Celaya | 1:2 | ||||
| 13. Round | 19/10/2021 | CF Monterrey II | - | Leones Negros | 0:1 | ||||
| 14. Round | 27/10/2021 | Leones Negros | - | Coyotes de Tlaxcala | 1:0 | |
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| 15. Round | 04/11/2021 | Venados FC | - | Leones Negros | 0:1 | ||||
| 16. Round | 14/11/2021 | Leones Negros | - | Cimarrones de Sonora | 3:2 | |
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| 17. Round | 18/11/2021 | Tepatitlán | - | Leones Negros | 2:1 |
Mexico