Argentina, rampant at home and leaders with 17 points from eight matches at the halfway stage in the nine-nation group, have managed one win in three away games before facing Chile in Santiago.
Ecuador, a point behind, will be looking for a first away win against Venezuela at Puerto La Cruz after taking all but one of their 16 points at home, benefiting from the thin air of Quito at 2,800 metres that troubles teams coming in from sea level.
Colombia, also on 16 points and in second place on goal difference, are the best away team with wins in Peru and Chile but they have a bye and will not play another qualifier until March.
Both Argentina and Ecuador need to address their away form as they will play five times on the road in their remaining eight matches.
Alejandro Sabella's Argentina, who made a weak start to the qualifiers including a shock defeat in Venezuela, are improving led by Lionel Messi, who scored twice in the 3-0 home victory over Uruguay on Friday.
But they played poorly and were lucky to take a point in a 1-1 draw in their last away match in Peru.
"Chile will be tough rivals. They need to win and climb positions to qualify for the World Cup," said Messi.
The Chileans are fifth, level on 12 points with Uruguay. Against Argentina they will be without defender Pablo Contreras and midfielder Arturo Vidal, who were sent off on Friday, and left-back Osvaldo Gonzalez who was booked.
Ecuador, who drew 1-1 in Uruguay last month, are well aware that dropping points away from home can damage their chances of reaching the finals for the third time since 2002.
"Thinking of just not losing the game would be mediocre. We work to win in any stadium," defender Frickson Erazo told reporters after the win over Chile.
"We know Venezuela is a very important game. They have evolved and can qualify for the World Cup too. We must show that we're a strong team not only in Quito," captain Walter Ayovi said.
VALENCIA RETURNS
Ecuador will be without suspended striker Felipe Caicedo, whose two goals against Chile took his tally to four, but winger Antonio Valencia returns.
Venezuela, who had a bye on Friday, are in sixth place with 11 points, one below the play-off berth. The top four will qualify for the 2014 finals in Brazil and the fifth will meet an Asian team for another berth.
Uruguay, well short of the form that took them to the 2010 World Cup semi-finals in South Africa and victory in last year's Copa America, need to improve after taking one point in the last three matches.
They face Bolivia in La Paz having to cope with the nearly 4,000-metre altitude and the suspensions of defenders Diego Lugano, Diego Godin and Maxi Pereira, who were booked against Argentina. They do, however, welcome back Alvaro Pereira.
It is a good chance for eighth-placed Bolivia, who have four points, to make home advantage count, which they have not with only one win in four matches in La Paz.
Seventh-placed Peru, who have eight points after holding Bolivia 1-1 in La Paz on Friday, visit bottom team Paraguay in Asuncion.
