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| 1st(1st leg) | Pumas UNAM | - | CF América | 0:0 (0:0) | ||
| 2nd (2nd leg) | CF América | - | Pumas UNAM | 1:3 (1:2) | ||
| 1st(1st leg): 25/11/2021 01:00 | 2nd (2nd leg): 28/11/2021 01:00 | Winner: Pumas UNAM | ||||
| 1st(1st leg) | CF Monterrey | - | Atlas Guadalajara | 0:0 (0:0) | ||
| 2nd (2nd leg) | Atlas Guadalajara | - | CF Monterrey | 1:1 (1:0) | ||
| 1st(1st leg): 25/11/2021 03:05 | 2nd (2nd leg): 28/11/2021 03:05 | Winner: CF Monterrey | ||||
| 1st(1st leg) | Puebla FC | - | Club León | 2:1 (1:1) | ||
| 2nd (2nd leg) | Club León | - | Puebla FC | 2:0 (1:0) | ||
| 1st(1st leg): 26/11/2021 01:00 | 2nd (2nd leg): 29/11/2021 02:05 | Winner: Club León | ||||
| 1st(1st leg) | Santos Laguna | - | UANL Tigres | 2:1 (2:0) | ||
| 2nd (2nd leg) | UANL Tigres | - | Santos Laguna | 1:0 (0:0) | ||
| 1st(1st leg): 26/11/2021 03:05 | 2nd (2nd leg): 29/11/2021 00:00 | Winner: UANL Tigres | ||||
