The match in Columbus, Ohio, is one of three which kick off the CONCACAF qualifying competition's final stage, a six-team mini-league from which the top three sides will qualify for South Africa 2010.
The fourth-placed side will get another bite of the cherry when they play off against the fifth team from South America.
Dwight Yorke, 37, will lead Trinidad & Tobago in El Salvador, where they will face a hostile reception, and Benfica striker David Suazo will spearhead Honduras's attack on the artificial pitch at Costa Rica's Saprissa stadium.
Eriksson's Mexico side scraped into the final stage on goal difference from Jamaica and the statistics are stacked against them.
Mexico have not won in their last 10 visits to the U.S., a run stretching back to 1998, and have only managed one win in their last six games.
Several of their forwards -- including Giovani dos Santos, Omar Bravo and Nery Castillo -- are short of match practice after struggling at club level in Europe while Arsenal's Carlos Vela is suspended.
The Mexican media are already calling for Eriksson's head barely six months after he replaced Hugo Sanchez, who himself lasted only 16 months in the hot seat.
The players have publicly stood up for the Swede and are determined to end a dismal run which has included defeats in Honduras and Jamaica.
AMERICAN DOMINANCE
"We are going to prove on the field that we are better," striker Carlos Ochoa told Mexican reporters in Columbus.
"This U.S. dominance has to end, we have to support Eriksson with a good result and by playing a good game."
"You will see a team with good discipline... and attitude, because we know that football-wise, we are good enough."
Honduras, who made their only World Cup appearance in 1982, will be missing key midfielder Wilson Palacios through suspension when they visit Costa Rica.
The Ticos, attempting to reach a third successive finals, are missing goalkeeper Keynor Navas, who suffered a training ground injury last week.
Trinidad, under Colombian coach Francisco Maturana, have included eight English-based players in their squad for their visit to El Salvador, who have been involved in several recent controversies.
Panama made an official protest after a World Cup qualifier to El Salvador last year, saying they were subjected to racist chants and were pelted with bags of urine.
Ten days ago, El Salvador, coached by former Mexico international Carlos de los Cobos, were forced to abandon their Central American championship semi-final against Costa Rica in the 60th minute.
They had two players sent off and then, having made the three permitted substitutions, suffered three injuries in quick succession, leaving them with only six players.
