Clint Dempsey gave the United States an early lead, but Honduras would rally back to leave the Americans without a point in the final round of World Cup qualifying.
Clint Dempsey put the Americans on the board in the 36th minute before Honduras responded with unanswered goals from Juan Garcia and Jerry Bengtson on either side of halftime.
It was the first time the U.S. had ever lost the opening game of the Hex and only the fourth time the Stars and Stripes had been defeated by Honduras in 19 games dating back to 1965.
"Overall, there were too many mistakes done and too many players today just didn't reach their usual potential," U.S. coach Jurgen Klinsmann said. "They stayed behind their own game and therefore, it's really difficult coming away with a win here if you're not having everybody 100 percent at their limits."
Playing in one of the most hostile atmosphere in CONCACAF to open the final stage of qualifying for the 2014 World Cup in Brazil, the Americans couldn't have gotten off to a more promising start.
Jermaine Jones delivered a beautiful chip over the top of the defensive line and found Dempsey who finished with a classy volley. It was Dempsey's 31st career goal with the national team, moving him up to third on the all-time scoring list while giving the U.S. hope early on.
But the celebration wouldn't last long.
It took just four minutes for Honduras to respond in remarkable fashion, with Garcia stunning goalkeeper Tim Howard with an bicycle kick from about 10 yards out. Following a misplaced corner kick, Honduras sent the ball back across the net twice before the defender elevated for the strike to enter the half all tied up.
The teams began the second half trading scoring opportunities, with Michael Bradley and Garcia watching their shots go just wide. Bengston had a golden chance to put Honduras ahead in the 55th minute after overpowering U.S. defender Geoff Cameron but his shot flew over the crossbar.
"We had problems closing down the passing lanes, also on the outsides throughout the whole first half and also in the second half," Klinsmann said.
With the U.S. back line on its heels, Honduras appeared to have taken the lead when Carlos Costly beat the defense before beating Howard. However, the goal would be waived off by the referee as Costly was just barely offside on the play.
The more the second half went on, the more the Americans looked like they were were content with picking up just a point on the road. That strategy, however, would get them in trouble.
In the 79th minute, Honduras would finally break the defensive wall for the game-winning goal. Some terrible defending by the USA's green center back pairing left Bengtson with a simple tap home for the winner.
The U.S. struggled to get possession in the final 10 minutes, but made things interesting three minutes into injury time when Omar Gonzalez headed a corner kick over the crossbar.
The U.S. will now have to wait until next month to bounce back with a home match against Costa Rica on March 22 followed by a visit to rival Mexico four days later.