Mexico suffered only their second ever qualifying defeat in the Azteca Stadium with a 2-1 loss to Honduras on Friday that increases the pressure on coach Jose Manuel de la Torre and leaves 'El Tri' with plenty of work to do to qualify for Brazil.
Costa Rica, who top the CONCACAF region standings, took a step towards booking their place at next year's finals with an impressive 3-1 win over the United States, while Panama were held to a goalless draw at home to Jamaica in the other game.
After seven rounds of matches, Costa Rica lead the way on 14 points with the United States on 13 and Honduras on 10, while Mexico sit in fourth place, outside the automatic qualification slots, on eight points in the final stage group.
Panama are on seven and Jamaica are bottom of the six-team standings on three points.
Mexico's biggest worry going into Friday's game was a lack of firepower at home after their three previous qualifiers at the Azteca had all ended in goalless draws.
Seeking to address the issue, De la Torre left Manchester United striker Javier Hernandez on the bench and started with Oribe Peralto in attack with the move paying off instantly.
Giovani dos Santos burst down the left flank and picked out Peralto with a low cross, which the striker calmly slotted home to end Mexico's home goal drought after just six minutes.
Mexico seemed in control but the introduction of Jerry Bengtson to the Honduran attack changed the game.
Carlos Costly's powerful drive was parried out by Jose Corona and Bengtson reacted quickly to tap in the loose ball for a 64th minute equalizer.
Two minutes later, Costly grabbed the winner when he bustled past Diego Reyes before unleashing a superb shot into the far corner.
De la Torre left the field to a chorus of "Chepo out, Chepo out" from the home crowd, who were demanding his resignation while chanting his nickname.
"To resign would be a failure, to fail is to stop fighting for things, we can't give up our project," he told reporters.
"Not to deliver adequate results is something that worries us, it's something mental we have to correct... We're in debt with everyone, with our football, and that's very worrying."
Mexico travel to Columbus, Ohio to face the United States on Tuesday with both teams feeling the pressure to get back to winning ways quickly.
The U.S. suffered a blow even before the game began when key midfielder Michael Bradley limped off the field with an ankle injury picked up during the warm-up.
Costa Rica grabbed the lead in the third minute when Jhonny Acosta headed in a corner at the near post past DaMarcus Beasley on the line.
Seven minutes later it was 2-0 when Cristian Bolanos floated a ball towards the back post and Celso Borges rose superbly above Beasley to head home.
Playing in his 100th international game, Clint Dempsey converted a penalty shortly before the break to give Juergen Klinsmann's side hope of a second half comeback.
But a goal on the breakaway by the lively Joel Campbell with 13 minutes remaining secured victory for Costa Rica.
Panama will be kicking themselves for not taking advantage of Mexico's stumble after they failed to defeat a Jamaica team that played most of the second half with 10 men.
It was the first game in charge for Jamaica's new German coach Winfried Schaefer and he had keeper Donovan Ricketts to thank for some superb saves.
Jamaica had Rodolph Austin sent off for a second bookable offence in the 58th minute but held on for a point.
(Additional reporting by Carlos Calvo in Mexico City; Reporting By Simon Evans; Editing by John O'Brien)