The last round of the CONCACAF Zone will see the top three teams qualify directly to next year's World Cup in Brazil, while the fourth-placed side will play a knockout tie with a South American nation.
Honduras managed to claim their very first home win over the USA in a World Cup qualification encounter.
It was not all plain sailing for the hosts, however, with Clint Dempsey putting Jurgen Klinsmann's men ahead with a volley in the 35th minute.
However, Juan Carlos Garcia equalised with a tremendous bicycle-kick four minutes later.
Honduras dominated thereafter in San Pedro Sula, but only clinched the winner in the 78th minute when Jerry Bengtson finished after some lovely work by Boniek Garcia.
Honduras boss Luis Fernando Suarez told reporters: "The win is quite nice but this is only the first step.
"The team did interesting things on the field and always went towards the rivals' goal. This is a totally deserved win and it is because the team played better."
United States' coach Klinsmann added: "We made lots of mistakes and another team played better than us. That team was Honduras today. Their two goals were very nice.
"The final score shocked us, even though we know playing Honduras home or away is very hard. Now we must win the next games because we must get into the World Cup."
In Panama City, hosts Panama were held to a 2-2 draw against Costa Rica, who were far from their best for large periods but hit back from two goals down to claim a share of the spoils.
Luis Henriquez put Panama ahead in the 14th minute after a Rolando Escobar throw-in, while Roman Torres made it 2-0 after a Marcos Sanchez cross.
Alvaro Saborio halved the deficit six minutes before half-time by heading home from Christopher Meneses' pass, while Bryan Ruiz levelled proceedings with seven minutes to go.
Elsewhere, Mexico were fortunate to come away with a goalless draw at home to Jamaica.
Mexico goalkeeper Jose de Jesus Corona was the man of the match after making several fine saves.
However, opposite number Donovan Ricketts was also kept busy, repelling two efforts from Manchester United striker Javier Hernandez.
Wednesday's 2014 FIFA World Cup (CONCACAF) Qualifying Results
Honduras 2-1 United States
Panama 2-2 Costa Rica
Mexico 0-0 Jamaica