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| H (Match allé) | Atlas Guadalajara | - | Deportivo Toluca | 3:0 (2:0) | ||
| R (match retour) | Deportivo Toluca | - | Atlas Guadalajara | 0:0 (0:0) | ||
| H (Match allé): 17.11.2021 16:00 | R (match retour): 20.11.2021 16:00 | vainqueur: Atlas Guadalajara | ||||
| H (Match allé) | UANL Tigres | - | CF América | 4:2 (3:1) | ||
| R (match retour) | CF América | - | UANL Tigres | 0:0 (0:0) | ||
| H (Match allé): 17.11.2021 16:00 | R (match retour): 20.11.2021 19:30 | vainqueur: UANL Tigres | ||||
| H (Match allé) | Mazatlán FC | - | Cruz Azul | 2:1 (1:0) | ||
| R (match retour) | Cruz Azul | - | Mazatlán FC | 4:1 (2:0) | ||
| H (Match allé): 17.11.2021 18:30 | R (match retour): 20.11.2021 16:00 | vainqueur: Cruz Azul | ||||
| H (Match allé) | Club León | - | Santos Laguna | 1:0 (0:0) | ||
| R (match retour) | Santos Laguna | - | Club León | 1:0 (0:0) | ||
| H (Match allé): 18.11.2021 16:00 | R (match retour): 21.11.2021 18:00 | |||||
