A fourth country in the six-team qualifying phase, bottom-placed Jamaica, also have a slim mathematical chance for the playoff spot against Oceania winners New Zealand but it is the battle for the last automatic spot that has garnered most attention.
With 11 points from their first eight matches, Honduras are the masters of their own destiny. They hold a three-point lead over Mexico and Panama and need just four points from their last two matches to be assured of reaching the World Cup finals for third time.
They could secure their spot as early as Friday if they beat Costa Rica and Mexico and Panama, who are due to meet in Mexico City, draw. Otherwise they will have to wait for Tuesday's final round of qualifiers.
"It is going to be a difficult game, they are going to come in here wanting to beat us," said Honduras defender Victor Bernardez.
"But for me, this is a great opportunity to give everything to qualify."
Of the four countries still trying to qualify, none is under more pressure than Mexico, traditionally the strongest team in the CONCACAF region that covers North and Central America and the Caribbean.
Mexico have qualified for every World Cup since 1982, with the exception of 1990 when they were banned by FIFA after fielding over-age players in a youth tournament.
But they have struggled to score throughout their latest qualifying campaign, finding the net just four times in their first eight matches, and are now on their third coach.
Jose Manuel 'Chepo' de la Torre was dismissed after a 2-1 home defeat by Honduras then his replacement, Luis Fernando Tena, stepped down after one game in charge when Mexico lost to the U.S.
Victor Vucetich has taken on the reins and signalled his intentions by recalling former Barcelona defender Rafael Marquez and newly-naturalised Argentine-born midfielder Lucas Lobos to his squad.
But Panama are on a mission of their own. They have never qualified for the World Cup before but are on a high after reaching the final of this year's CONCACAF Gold Cup.
"We're not going to let this great opportunity escape us," said Dely Valdes, one of Panama's best players.
There is little at stake for the U.S. in their match against Jamaica in Kansas City although a defeat could keep the visitors in the hunt for the playoff spot although the odds are heavily stacked against them, needing to win their last two games and have other results go their way.
(Reporting by Julian Linden in New York; editing by Toby Davis)
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