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| H (Match allé) | CF Pachuca | - | Atlas Guadalajara | 0:2 (0:1) | ||
| R (match retour) | Atlas Guadalajara | - | CF Pachuca | 3:2 (2:0) | ||
| H (Match allé): 04.05.2022 17:00 | R (match retour): 07.05.2022 16:00 | vainqueur: Atlas Guadalajara | ||||
| H (Match allé) | Pumas UNAM | - | CF América | 3:0 (1:0) | ||
| R (match retour) | CF América | - | Pumas UNAM | 2:1 (2:0) | ||
| H (Match allé): 04.05.2022 17:00 | R (match retour): 07.05.2022 18:30 | vainqueur: Pumas UNAM | ||||
| H (Match allé) | Deportivo Guadalajara | - | Santos Laguna | 4:1 (3:1) | ||
| R (match retour) | Santos Laguna | - | Deportivo Guadalajara | 4:1 (1:0) | ||
| H (Match allé): 05.05.2022 18:15 | R (match retour): 08.05.2022 17:00 | |||||
| H (Match allé) | Club Tijuana | - | Club León | 3:2 (2:2) | ||
| R (match retour) | Club León | - | Club Tijuana | 0:3 (0:1) | ||
| H (Match allé): 05.05.2022 21:45 | R (match retour): 08.05.2022 18:30 | vainqueur: Club Tijuana | ||||
