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| H | Pumas UNAM | - | CF América | 0:0 (0:0) | ||
| R | CF América | - | Pumas UNAM | 1:3 (1:2) | ||
| H: 25.11.2021 02:00 | R: 28.11.2021 02:00 | Sieger: Pumas UNAM | ||||
| H | CF Monterrey | - | Atlas Guadalajara | 0:0 (0:0) | ||
| R | Atlas Guadalajara | - | CF Monterrey | 1:1 (1:0) | ||
| H: 25.11.2021 04:05 | R: 28.11.2021 04:05 | Sieger: CF Monterrey | ||||
| H | Puebla FC | - | Club León | 2:1 (1:1) | ||
| R | Club León | - | Puebla FC | 2:0 (1:0) | ||
| H: 26.11.2021 02:00 | R: 29.11.2021 03:05 | Sieger: Club León | ||||
| H | Santos Laguna | - | UANL Tigres | 2:1 (2:0) | ||
| R | UANL Tigres | - | Santos Laguna | 1:0 (0:0) | ||
| H: 26.11.2021 04:05 | R: 29.11.2021 01:00 | Sieger: UANL Tigres | ||||
