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| 1st(1st leg) | Deportivo Toluca | - | CF América | 0:1 (0:0) | ||
| 2nd (2nd leg) | CF América | - | Deportivo Toluca | 4:0 (1:0) | ||
| 1st(1st leg): 04/05/2022 15:00 | 2nd (2nd leg): 07/05/2022 15:30 | Winner: CF América | ||||
| 1st(1st leg) | Deportivo Guadalajara | - | Club Tijuana | 0:2 (0:1) | ||
| 2nd (2nd leg) | Club Tijuana | - | Deportivo Guadalajara | 1:0 (1:0) | ||
| 1st(1st leg): 05/05/2022 15:00 | 2nd (2nd leg): 09/05/2022 03:00 | Winner: Club Tijuana | ||||
| 1st(1st leg) | Santos Laguna | - | Club León | 1:0 (0:0) | ||
| 2nd (2nd leg) | Club León | - | Santos Laguna | 5:2 (2:0) | ||
| 1st(1st leg): 05/05/2022 17:00 | 2nd (2nd leg): 08/05/2022 15:00 | Winner: Club León | ||||
| 1st(1st leg) | UANL Tigres | - | CF Pachuca | 4:2 (2:0) | ||
| 2nd (2nd leg) | CF Pachuca | - | UANL Tigres | 1:0 (1:0) | ||
| 1st(1st leg): 05/05/2022 17:00 | 2nd (2nd leg): 08/05/2022 18:00 | Winner: UANL Tigres | ||||
