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 contest, which consisted of predominately locally based players, was a tentative affair in the opening minutes.
Fans in attendance were finally treated to a shot on target in the 13th minute when USA defender Omar Gonzalez forced opposition goalkeeper Moises Munoz into a finger-tip save.
Bradley, who returned home to MLS after eight years in Europe, sent the fans into raptures just seconds later after finding the back of the net from the resulting corner.
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.
Bradley picked out Wondolowski with a superb header and the San Jose Earthquakes star made no mistake inside the box, firing a right-footed shot past a helpless Munoz.
Whatever Herrera said during the half-time break worked a treat as Mexico restored parity with just over 20 minutes remaining.
Marquez found himself unmarked inside the penalty area to head home a bullet header five minutes in the second stanza before Pulido tucked away a rebound on 67 minutes - his fourth goal in three games following his hat-trick against South Korea in January.
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.
The USA will not be in action again until April 27 when they host minnows Azerbaijan, while Mexico face Israel the following day.
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