Mexico go into the match lying in fourth place in the six-nation final group, from which three teams advance directly to South Africa 2010. The fourth-placed team must play off against a team from South America for a berth.
Costa Rica leads North American regional qualifying with 12 points to ten for the United States. Honduras is third with Mexico in fourth. Mexico received a massive morale boost heading into the match with a 5-0 victory over the United States in the CONCACAF Gold Cup final on 26 July.
But that was against a young USA side that didn't include stars such as Landon Donovan. On Wednesday USA coach Bob Bradley will field a full-strength team as the Americans vie for a first-ever victory over Mexico at Azteca. They have only managed one draw there - a goalless draw in a 1997 FIFA World Cup qualifier.
"The difficulty is everything but the soccer," Donovan said of the challenge of taking on Mexico at Azteca - where the altitude, poor air quality and fiercely partisan crowd of 100,000 all play a role. "They use all of the outside influences to their advantage, but that's not an excuse anymore for us. We're not going to use it as an excuse.
"We're not going for a point," Donovan said. "We're going there to win the game and we're going to keep playing the way we're playing." Donovan was referring to the form that has seen the United States win three of their five qualifiers to date, and reach the final of the FIFA Confederations Cup in South Africa.
Bradley has recalled a number of players who skipped the Gold Cup, including defender Oguchi Onyewu of AC Milan, Fulham midfielder Clint Dempsey, Hull City's Jozy Altidore and the Los Angeles Galaxy's Donovan.
Mexico coach Javier Aguirre's squad includes his Gold Cup champions along with defender Carlos Salcido (PSV Eindhoven), Andres Guardado (Deportivo La Coruna) and veteran Cuauhtemoc Blanco (Chicago Fire). Aguirre replaced Sven Goran Eriksson in April and after a defeat at El Salvador saw his side down Trinidad and Tobago in FIFA World Cup qualifying on 10 June.
Despite Mexico's struggles in this qualifying campaign, Aguirre insists his side have what it takes. "It's not a dark scenario," he said. "Why the heck were we going to be out of the World Cup? They have to give us a chance. If there was one game left and we had to win and have two rivals lose, then I would say it was tough. But things are different. Things have improved."
Costa Rica will be trying to maintain their spot atop the standings when they travel to Honduras, while Trinidad and Tobago host El Salvador. Honduras coach Reinaldo Rueda, who also turned to a young squad in the Gold Cup, has recalled his best to take on the Ticos in the Estadio Olimpico Metropolitano in San Pedro Sula.
David Suazo of Inter Milan is still out with a leg injury, but Rueda has the services of captain Amado Guevara from Toronto FC, Tottenham midfielder Wilson Palacios, Parma's Julio de Leon, Carlo Costly and Carlos Pavon. Honduras have seven points from five matches. While they are lying third, they are three points behind USA, just one in front of Mexico and only two ahead of El Salvador - who will be seeking to gain ground at winless Trinidad and Tobago.