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| 1st(1st leg) | Atlas Guadalajara | - | Deportivo Toluca | 3:0 (2:0) | ||
| 2nd (2nd leg) | Deportivo Toluca | - | Atlas Guadalajara | 0:0 (0:0) | ||
| 1st(1st leg): 17/11/2021 15:00 | 2nd (2nd leg): 20/11/2021 15:00 | Winner: Atlas Guadalajara | ||||
| 1st(1st leg) | UANL Tigres | - | CF América | 4:2 (3:1) | ||
| 2nd (2nd leg) | CF América | - | UANL Tigres | 0:0 (0:0) | ||
| 1st(1st leg): 17/11/2021 15:00 | 2nd (2nd leg): 20/11/2021 18:30 | Winner: UANL Tigres | ||||
| 1st(1st leg) | Mazatlán FC | - | Cruz Azul | 2:1 (1:0) | ||
| 2nd (2nd leg) | Cruz Azul | - | Mazatlán FC | 4:1 (2:0) | ||
| 1st(1st leg): 17/11/2021 17:30 | 2nd (2nd leg): 20/11/2021 15:00 | Winner: Cruz Azul | ||||
| 1st(1st leg) | Club León | - | Santos Laguna | 1:0 (0:0) | ||
| 2nd (2nd leg) | Santos Laguna | - | Club León | 1:0 (0:0) | ||
| 1st(1st leg): 18/11/2021 15:00 | 2nd (2nd leg): 21/11/2021 17:00 | |||||
