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| 1st(1st leg) | Puebla FC | - | CF América | 1:1 (0:0) | ||
| 2nd (2nd leg) | CF América | - | Puebla FC | 3:2 (1:1) | ||
| 1st(1st leg): 11/05/2022 03:05 | 2nd (2nd leg): 15/05/2022 00:00 | Winner: CF América | ||||
| 1st(1st leg) | Atlético San Luis | - | CF Pachuca | 2:2 (1:1) | ||
| 2nd (2nd leg) | CF Pachuca | - | Atlético San Luis | 3:2 (0:0) | ||
| 1st(1st leg): 12/05/2022 01:00 | 2nd (2nd leg): 15/05/2022 02:05 | Winner: CF Pachuca | ||||
| 1st(1st leg) | Cruz Azul | - | UANL Tigres | 0:1 (0:1) | ||
| 2nd (2nd leg) | UANL Tigres | - | Cruz Azul | 0:1 (0:1) | ||
| 1st(1st leg): 13/05/2022 01:00 | 2nd (2nd leg): 16/05/2022 02:05 | |||||
| 1st(1st leg) | Deportivo Guadalajara | - | Atlas Guadalajara | 1:2 (0:2) | ||
| 2nd (2nd leg) | Atlas Guadalajara | - | Deportivo Guadalajara | 1:1 (1:0) | ||
| 1st(1st leg): 13/05/2022 03:05 | 2nd (2nd leg): 16/05/2022 00:00 | Winner: Atlas Guadalajara | ||||
