Brek Shea, who entered two minutes earlier, went down the left flank and around Severo Meza. Shea, back with the national team after being dropped for six months, crossed to Terrence Boyd. He made a quick backheel pass to Orozco Fiscal, who had entered in the 77th
Orozco Fizcal, who plays in Mexico for San Luis, kicked the ball past goalkeeper Guillermo Ochoa for his first international goal.
Tim Howard preserved the lead, changing directions to stop a deflected shot by Javier Hernandez in the 85th, then pawing away a 4-yard downward header by Chicharito in the 89th.
The U.S. had been 0-23-1 against El Tri in 75 years of games at Mexico, including 0-19-1 in the thin air at altitude in Mexico City - where they have been outscored 81-14.
It was the second big win for the Americans this year, following their first-ever victory over Italy in a friendly at Genoa in February.
With the European clubs seasons getting under way, the U.S. used a half-strength roster and a makeshift central defense.
Mexico, also below strength following the Olympics, dominated possession but failed to connect on several open shots as the Americans paired Maurice Edu and Geoff Cameron in the center of their back line.
The game marked the start of the Americans' second year under coach Jurgen Klinsmann, who replaced Bob Bradley last summer after Mexico overcame
The U.S. figures to have a lineup closer to full strength for a pair of World Cup qualifiers against Jamaica next month, on the road on Sept. 7 and at Columbus, Ohio, four days later. Mexico plays Costa Rica twice on those same days.
Landon Donovan, searching for his 50th international goal, left at the start of the second half because of a tight hamstring and DaMarcus Beasley came in for his 97th international appearance. Boyd came in at the same time to replace an ineffective Jose Torres.
Cameron got his head on a cross from Elias Hernandez in the 56th minute, preventing Hernandez from an open shot in front. A minute later, Jesus Zavala put an open header over the crossbar.
With Ochoa off his line, Kyle Beckerman put a long, sliding shot just over the crossbar in the 60th.
Andres Guardado hooked a free kick just wide to Howard's right post in the 65th after Cameron fouled Hernandez just outside the penalty area. Hernandez then sent an open header wide in the 76th off a cross from Hernandez.