Skipper Rafael Marquez scored an 89th minute winner as Mexico stunned the United States 2-1 in a thrilling World Cup qualifying duel between the arch-rivals here Friday.
Marquez, 37, headed home a Miguel Layun corner in the dying minutes of a pulsating battle which saw an ugly scuffle deep into injury time.
Marquez's goal came after the US had clawed their way back into the contest with a Bobby Wood equaliser on 49 minutes after Layun's 20th-minute goal put Mexico 1-0 up.
Jurgen Klinsmann's side had looked the likeliest to take all three points but instead it was Marquez who struck to snatch Mexico's first ever qualifying win over the United States at their Columbus stronghold.
The result gives Mexico the early initiative in the CONCACAF region's six-team final round of qualifying for the 2018 World Cup in Russia.
The United States now face a testing trip to Costa Rica on Tuesday needing to pick themselves up after a shattering loss.
Mexico had the better of a frenetic first half, rattling US nerves after only 10 minutes when Jesus Corona cut in from the left and saw his shot tipped against the woodwork after a diving save from Tim Howard.
At the other end, the US threatened sporadically but were unable to find the breakthrough, with Jozy Altidore's 20th minute header easily gathered by Mexico goalkeeper Alfredo Talavera.
Moments later Mexico took the lead. Again it was an attack that began down the left flank, Layun pouncing on a loose ball near the edge of the area and driving a low shot which took a slight deflection as it flew past Howard.
The US were rocking and Mexico almost doubled their tally five minutes later when Corona's cross was met with a glancing header from Carlos Vela which crashed back off the crossbar.