Tigres UANL stunned Cruz Azul 3-0 as Luis Tena's men saw their lead at the top cut to just three points.
Juninho opened the scoring in the eighth minute with a well-struck penalty, and it was 2-0 just before the half-hour mark.
Alan Pulido lost his marker and headed in from close range as Cruz Azul uncharacteristically let themselves down in defence.
Carlos Salcido was sent off for hosts Tigres UANL on 65 minutes, but they still managed a third through United States international Jose Francisco Torres.
Cruz Azul had conceded just three goals in nine league games heading into the encounter, yet Tigres UANL were far too good.
Toluca took their chance to close the gap by claiming a 3-0 win at home to Puebla.
Brazilian Wilson Mathias tapped in a 27th-minute opener after a set-piece before Raul Nava tucked away a penalty early in the second half.
Carlos Esquivel scored the pick of the goals 12 minutes before full-time with a thunderous 30-yard strike into the top corner.
Michael Arroyo was a four-goal hero for Atlante, leading his side to a 4-2 victory over Queretaro.
Enner Valencia built on his goal for Ecuador in their mid-week win over Australia by netting a brace to lead Pachuca to a 2-0 victory over a Monterrey side who finished with nine men.
Pumas UNAM suffered a 3-1 loss at Morelia after giving up a lead while America lost again, beaten 4-2 by Santos Laguna.
Leon conceded late to lose 1-0 at home to Veracruz, Tijuana overcame Guadalajara 2-0 and Carlos Ochoa's brace helped Chiapas fight back for a 2-2 draw at Atlas.
