Honduras will host the match in San Pedro Sula where rivalry on the field will be intense with both teams attempting to reach their first World Cup since 1982 and only one point separating them in the final stage of the CONCACAF tournament.
Honduras are fourth in the six-team group with four points from four games, one place below El Salvador who controversially beat Mexico 2-1 on Saturday with a late penalty.
The top three teams qualify directly for next year's finals in South Africa and the fourth will play off against the fifth team from South America, currently Uruguay, for another place.
Troubled Mexico, fifth with three points, host table-propping Trinidad and Tobago (2) at the Azteca in Wednesday's other match.
Leading pair Costa Rica (12 points from five games) and the United States (10 from five), who do not play, appear to be cruising towards South Africa, leaving the other four to scrap for the remaining direct place and the playoff spot.
Matches between Honduras and El Salvador inevitably revive memories of the 100-hours war which the countries fought following a series of three World Cup qualifiers in 1969.
Mutual hatred surfaced at the first game in Tegucigalpa when Salvadorean fans taunted victorious Honduran players after their 1-0 win, fuelling political tensions between the two countries over Salvadorean immigrants in Honduras.
One week later, rival fans fought and cars were torched as El Salvador won the return match 3-0 in San Salvador.
MILITARY ACTION
El Salvador then won a playoff in Mexico City 3-2 but Honduras said they had been cheated. Hostilities quickly flared into a diplomatic stand-off and then full-on military action as El Salvador attacked Honduras.
Neither side won a decisive military victory, 5,000 people died and a ceasefire was quickly called although the squabble was not formally buried until 2006, when the presidents of the two countries stood on the border and shook hands.
"Honduras is definitely under more pressure for this game," said El Salvador's Mexican coach Carlos de los Cobos.
"They've just lost to the United States and have the duty to win at home in front of their supporters to keep totting up points. We have to play this game in an intelligent way."
Honduras, coached by Colombian Reinaldo Rueda, are missing injured striker David Suazo.
Mexico should pick up three points at home to the Soca Warriors.
Coach Javier Aguirre, brought back for a second stint after Sven-Goran Eriksson was fired in April, says that, with four of their last six games at home, their predicament is not as bad as it looks.
Captain Pavel Pardo and midfielder Gerardo Torrado will both miss the game through suspension while Rafael Marquez is out with a long-term injury.
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