Juergen Klinsmann's US team share the lead in CONCACAF qualifying group A with Jamaica and head to Kingston after picking up four points from their opening two games.
After being surprisingly held to a 1-1 draw in Guatemala, the US gained a much-needed 3-1 victory at home to Antigua and Barbuda in June.
With the top two teams from each of the three groups making it to the fourth round of qualifying, starting in February, the US and Jamaica should be confident of progressing.
But they are eager to get a psychological edge for what should be a fiercely contested battle for three places at the 2014 finals in Brazil from North and Central America and the Caribbean.
"It's huge, it's a six-point opportunity but it's going to be difficult though, the guys know that," said Klinsmann, whose team were boosted by a friendly win against Mexico at the Azteca Stadium last month.
"You look at Jamaica their team, their individuals, they have a lot of quality and a lot of speed. But we should be confident because we did well in Mexico. The team is growing, the chemistry is good and the goal is to win in Jamaica," he said.
The US, whose four previous qualifiers in Jamaica have ended in draws, will be without injured record goalscorer Landon Donovan and AS Roma midfielder Michael Bradley - two major absentees.
But Klinsmann could feature forward Clint Dempsey who has just moved from Fulham to Tottenham Hotspur, either in Kingston or in the return game in Columbus, Ohio on Tuesday.
Jamaica have never beaten the US in 18 competitive fixtures but coach Theodore Whitmore, who has overseen some steady improvements since taking charge of the team on a permanent basis in 2009, says the past counts for little.
"None of that matters. We know what the job at hand is, we know it is a tough one and that the US will have done their homework. So have we and we have to go out and execute the plan and win," he told the Jamaica Gleaner.
Mexico, with two wins from two in Group B, travel to San Jose to face Costa Rica on Friday and then host the Ticos at the Azteca Stadium on Tuesday. Despite the friendly loss to the US, El Tri are still basking in their London Olympics success.
Coach Jose Manuel de la Torre has called up eight members of the gold medal-winning team who beat Brazil in the Olympic final, including Manchester United striker Javier Hernandez.
However El Tri will be without midfielder Pablo Barrera who has suffered an anterior cruciate ligament injury and will be sidelined for up to six months.
Costa Rica, whose 2-2 draw at home to El Salvador leaves them with plenty of work to do on four points, will feature Bryan Oviedo at left back after he joined Premier League team Everton.
Group C could be the most tightly contested with Panama, who have a maximum six points from their opening two games, facing a double-header with Canada.
The improving Canadians are in second place with four points but know they cannot afford to slip up with Honduras expecting to pick up all three points against bottom side Cuba.