First-half goals from Michael Bradley and Chris Wondolowski had the USA on course for a routine victory at the University of Phoenix Stadium.
But Miguel Herrera's half-time team talk spurred Mexico into action as the visitors ensured honours were even courtesy of Rafael Marquez and Alan Pulido.
Despite avoiding defeat, Mexico remain winless in their past five encounters against Jurgen Klinsmann's USA team, with their last triumph a 4-2 victory in the 2011 CONCACAF Gold Cup.
The Toronto midfielder latched on to Graham Zusi's cross for his first international goal since the USA's 2-2 draw with Russia in 2012.
That goal sparked the contest into life and Mexico came close to levelling the scores on 23 minutes, however, Miguel Layun's long-range effort flashed agonisingly wide of the top corner.
As Herrera's team went in search of an equaliser, their woes were compounded five minutes later after Wondolowski doubled the home side's advantage.
The hosts thought they had the match won in the closing stages after substitute Eddie Johnson ran in behind Mexico's defence and netted.
But the DC United striker was controversially deemed offside, much to the disappointment of Klinsmann, who will be determined to address his team's defensive frailties ahead of the upcoming FIFA World Cup.
