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| 1st(1st leg) | CF Pachuca | - | Atlas Guadalajara | 0:2 (0:1) | ||
| 2nd (2nd leg) | Atlas Guadalajara | - | CF Pachuca | 3:2 (2:0) | ||
| 1st(1st leg): 04/05/2022 16:00 | 2nd (2nd leg): 07/05/2022 15:00 | Winner: Atlas Guadalajara | ||||
| 1st(1st leg) | Pumas UNAM | - | CF América | 3:0 (1:0) | ||
| 2nd (2nd leg) | CF América | - | Pumas UNAM | 2:1 (2:0) | ||
| 1st(1st leg): 04/05/2022 16:00 | 2nd (2nd leg): 07/05/2022 17:30 | Winner: Pumas UNAM | ||||
| 1st(1st leg) | Deportivo Guadalajara | - | Santos Laguna | 4:1 (3:1) | ||
| 2nd (2nd leg) | Santos Laguna | - | Deportivo Guadalajara | 4:1 (1:0) | ||
| 1st(1st leg): 05/05/2022 17:15 | 2nd (2nd leg): 08/05/2022 16:00 | |||||
| 1st(1st leg) | Club Tijuana | - | Club León | 3:2 (2:2) | ||
| 2nd (2nd leg) | Club León | - | Club Tijuana | 0:3 (0:1) | ||
| 1st(1st leg): 05/05/2022 20:45 | 2nd (2nd leg): 08/05/2022 17:30 | Winner: Club Tijuana | ||||
