Reigning Copa Libertadores champions Corinthians had a bad night in their bid to retain the continental title as they lost 1-0 at Tijuana.
The current Mexican champions consolidated their lead in Group 5 thanks to their victory.
Captain Javier Gandolfi netted the winner with a back-heel 21 minutes into the second half following a Fernando Arce free-kick.
The goal by the Argentinian defender left the FIFA Club World Cup winners second in the group standings on four points, five below Tijuana.
Tijuana boss Antonio Mohamed said: "This team keeps giving me surprises.
"We are proud of beating the world champions, we were fair winners.
"In this team, each player would risk their lives for the other. We never give up. This is the proof that we want to keep making history."
The reverse was Corinthians' first defeat in 16 Copa Libertadores matches.
Corinthians midfielder Ralf told reporters in Mexico that playing on artificial grass was hard but not an excuse.
He said: "It is difficult, quite horrible, but it is not a reason (for the loss).
"We lost because we failed to score goals, not because of the field."
Paraguay's Libertad came back from a two-goal deficit to draw 2-2 with Peruvian champions Sporting Cristal at home.
The draw leaves Libertad on top of Group 2 on seven points, three above Sporting Cristal.
Irven Avila opened the scoring for the visitors in the 21st minute and doubled the advantage after 64 following a Junior Ross pass.
Pedro Benitez reduced the deficit three minutes later and Jose Ariel Nunez levelled with only three minutes to go.
In another Group 2 match, a last-gasp goal by midfielder Gabriel Penalba saw Argentinian side Tigre beat Brazilian giants Palmeiras 1-0 at home.
It was a very tough game in the northern suburbs of Buenos Aires city and Tigre played the last nine minutes with 10 men after midfielder Vilson was sent off.
In the fourth minute of injury time, Botta sent a free-kick into the box, Diego Ferreira headed the ball and Penalba sent it into the back of the net.
The win took Tigre level with Palmeiras on three points, only one less than Sporting Cristal.
In Group 8, Fluminense took sole lead despite a disappointing 1-1 home draw with Chile's Huachipato.
The Brazilian champions wasted a number of chances after Fred opened the scoring in the 30th minute from the penalty spot.
Francisco Arrue dribbled past two Fluminense defenders and shot with 20 minutes to go.
Fluminense defender Gum failed to clear and Nicolas Nunez equalised.
Fluminense head the group standings on seven points, one above compatriots Gremio, who will complete the fourth matchday of this group next week against rock-bottom Caracas in Venezuela. Huachipato lie third on four points.
Mexican hosts Toluca picked up a point as they drew 1-1 with visitors Barcelona of Ecuador.
Argentinian playmaker Damian Diaz put Barcelona ahead in the 35th minute, while Panamanian striker Luis Tejada equalised by heading in an Edy Brambila cross with seven minutes to go.
Toluca join Uruguayan giants Nacional on top of Group 1 with four points, but Nacional still have to play their third group match against Boca Juniors.
Barcelona remain at the bottom on two points.
