Cruz Azul advanced to the semi-finals of the CONCACAF Champions League on Wednesday after thrashing Sporting Kansas City 5-1 to triumph 5-2 on aggregate, while Leon defeated Emelec 3-0 in the Copa Libertadores to move top of their group.
Matias Britos, Jose Vasquez and Carlos Pena scored Leon's goals against Emelec, while Mariano Pavone struck a hat-trick for Cruz Azul.
Leon's win ended their losing streak at three games and Gustavo Matosas' men will hope it can inspire them against the Liga MX leaders on Saturday.
Cruz Azul are flying high in the Mexican league with nine wins from 11 games in the Clausura campaign, but they have lost their past two away games in all competitions, which could give Leon something to work with.
Leon have won three of their past four matches at home and sit 10th in Liga MX on 14 points - exactly half of Cruz Azul's total.
The other Mexican clubs involved in continental competition this week - Santos Laguna, Toluca and Tijuana - also tasted success.
Santos Laguna trumped Deportivo Anzoategui 3-0 in the Copa Libertadores to extend their unbeaten run in all competitions to four games but will need to refocus quickly ahead of a trip to Morelia on Friday, while Tijuana will host Puebla after overcoming Los Angeles Galaxy 4-3 on aggregate in the Champions League quarter-finals.
Toluca edged out San Jose Earthquakes in a penalty shootout to reach the final four of the Champions League and will line-up against Atlante on Sunday.
In other games, America will welcome Veracruz to Mexico City, Tigres UANL face Queretaro, Pachuca take on Chiapas, Atlas will clash with Guadalajara and Monterrey will visit Pumas UNAM.
