Argentine striker Mariano Pavone, unlikely to break into his country’s star-studded World Cup attack, put them three up on the stroke of halftime.
Mexican Olympic goal medal winner Marco Fabian rounded off the victory 11 minutes from the end with his first goal for the club after joining on loan from Guadalajara in the mid-season break.
Cruz Azul, celebrating 50 years in the top flight, are unbeaten with 10 points from four matches.
America kept in close touch one point behind with a 2-1 away win over Atlas at the Jalisco in Guadalajara thanks to a double from their former Colombia defender Luis Gabriel Rey.
Title holders Leon, winners of the Apertura in the first half of the season, crashed to a second consecutive defeat going down 3-1 at home to Pachuca.
Ecuadoreans Enner Valencia, with a brace, and Alex Colon scored for Veracruz with Argentine striker Mauro Boselli pulling back a late consolation from the penalty spot.
UNAM Pumas, who finished bottom of the Apertura standings, upset 10-man UANL Tigres 2-1 away with a second half brace from Argentine-born Mexico striker Martin Bravo for only their second win in 21 matches this season.
Tigres had taken an early lead through Argentine Guido Pizarro but were reduced to 10 men in the 38th minute when Jose Rivas was sent off for elbowing an opponent.
Argentine defender Javier Gandolfi scored the only goal as Tijuana beat Morelia 1-0 on Friday. The border town team are on seven points with Pachuca, Queretaro and Toluca, who can join Cruz Azul on 10 if they beat Monterrey at home on Sunday.
(Writing by Rex Gowar in London; editing by Justin Palmer)