Table-toppers America and second-placed Santos Laguna are already guaranteed top-eight finishes and the onus is now on the sides below them to follow suit.
Leon are in pole position to join America and Santos Laguna and will be assured of progressing if they beat ninth-placed Tigres UANL on Sunday.
A win would also secure Leon's place in the 2014 Copa Libertadores.
However, Gustavo Matosas' men have hit a slight blip in form, having lost 2-0 at Queretaro on October 6 before being held 2-2 at home to Toluca last time out.
Toluca will be assured of a play-off place should they record a home victory over Atlas and Tigres fail to win.
Jose Cardozo's charges are unbeaten in six league games and will start as favourites at the Estadio Nemesio Diez.
Cruz Azul, meanwhile, welcome a Morelia outfit that could also book their place in the Apertura with victory on Saturday.
Azul have gone five games without defeat in the league, drawing their last two.
Elsewhere on Saturday, Veracruz must beat Monterrey to have any realistic chance of reaching the play-offs.
Tijuana's outside hopes will be brought to an end if they are beaten by visiting Atalante, while league leaders America face a visit to Queretaro
Chiapas will try to firm up their Apertura hopes at home to Santos Laguna on the following day, while 11th-placed Puebla face Pachuca knowing nothing less than victory will do and Guadalajara play fellow strugglers Pumas UNAM.
