The United States will miss their first World Cup since 1986 after a 2-1 defeat to Trinidad and Tobago - as Panama secured their debut appearance at the tournament next summer.
Bruce Arena's side started the day in pole position to secure the last of three qualifying spots, joining Mexico and Costa Rica in Russia, but a loss to the already-eliminated Trinidadians dashed hopes of an eighth straight appearance.
The US players sunk to the ground at the final whistle as other results in the group did not go their way.
Omar Gonzalez was put under pressure with a cross into the danger area and put the ball past Tim Howard on 17 minutes and Alvin Jones doubled the lead with a stellar long-range strike just before half-time.
Christian Pulisic got one back after the break, but the US pressure did not pay off.
The US were still sitting pretty as Costa Rica went ahead against Panama when Johan Venegas scored a cheeky dink on 36 minutes.
There was controversy for the equaliser - the referee judging Gabriel Torres's effort made it over the line despite protests from the Costa Ricans.
But there was no doubt about the winner on 88 minutes, when Roman Torres took the ball on the bounce and smashed it in from close range.
In the other group fixture, Honduras set up a tie against Australia with a 3-2 win over visitors Mexico in San Pedro Sula.
The home side found themselves 2-1 down at half-time, but an own goal from Guillermo Ochoa on 53 minutes and a Romell Quioto goal seven minutes later booked a two-legged play-off against the Socceroos in November.