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| 1st(1st leg) | TM Fútbol Club | - | Atlético Morelia | 2:2 (0:1) | ||
| 2nd (2nd leg) | Atlético Morelia | - | TM Fútbol Club | 0:2 (0:1) | ||
| 1st(1st leg): 01/12/2021 01:00 | 2nd (2nd leg): 04/12/2021 23:00 | Winner: TM Fútbol Club | ||||
| 1st(1st leg) | Leones Negros | - | Club Celaya | 1:0 (0:0) | ||
| 2nd (2nd leg) | Club Celaya | - | Leones Negros | 3:0 (2:0) | ||
| 1st(1st leg): 01/12/2021 03:05 | 2nd (2nd leg): 05/12/2021 23:00 | Winner: Club Celaya | ||||
| 1st(1st leg) | Tepatitlán | - | Dorados de Sinaloa | 0:1 (0:0) | ||
| 2nd (2nd leg) | Dorados de Sinaloa | - | Tepatitlán | 1:0 (0:0) | ||
| 1st(1st leg): 02/12/2021 01:00 | 2nd (2nd leg): 05/12/2021 01:05 | Winner: Dorados de Sinaloa | ||||
| 1st(1st leg) | Venados FC | - | Atlante | 0:2 (0:1) | ||
| 2nd (2nd leg) | Atlante | - | Venados FC | 0:0 (0:0) | ||
| 1st(1st leg): 03/12/2021 01:00 | 2nd (2nd leg): 05/12/2021 18:00 | Winner: Atlante | ||||
