*Cruz Azul 2-1 CF Montréal
| 17.03.2022 | CF Montréal | 1-1 | Cruz Azul | |
| 10.03.2022 | Cruz Azul | 1-0 | CF Montréal | |
New England Revs 3-3 UNAM Pumas *
| 17.03.2022 | UNAM Pumas | 3-0/p.4-3 | New England Revs | |
| 10.03.2022 | New England Revs | 3-0 | UNAM Pumas | |
*New York City FC 5-5 CSD Comunicaciones
| 16.03.2022 | CSD Comunicaciones | 4-2 | New York City FC | |
| 09.03.2022 | New York City FC | 3-1 | CSD Comunicaciones | |
*Seattle Sounders 4-1 Club León
| 18.03.2022 | Club León | 1-1 | Seattle Sounders | |
| 09.03.2022 | Seattle Sounders | 3-0 | Club León | |