Diego Forlan, Golden Ball winner as the 2010 World Cup's best player, has been dropped for Uruguay's critical qualifier away to Chile on Tuesday.
Top Serie A scorer Edinson Cavani, a substitute in Uruguay's disappointing 1-1 draw at home to Paraguay on Friday, was named instead by coach Oscar Tabarez on Monday to partner Luis Suarez up front.
"We need to improve a lot in what the team does when they take possession of the ball," Tabarez told a news conference in Santiago following Uruguay's last practice on Chilean soil.
To this end, Tabarez picked Gaston Ramirez in place of Cristian Rodriguez to add ball possession and creativity in midfield.
Suarez scored all four goals when Uruguay were in better form and crushed Chile 4-0 in Montevideo in November 2011.
The South American champions have struggled for goals in their last five qualifiers, scoring only three and taking just two points.
They are not noted for their generosity at the back but have shipped 13 goals in five matches and 19 in 10 overall, the worst defence along with Chile and Bolivia.
"We've committed a lot of defensive errors that cost us points. A performance often is related to results [and] a positive result is what can change everything at the moment," said Tabarez.
"We need points urgently because we are among several teams fighting for the fourth and fifth place," Tabarez said.
Uruguay are fourth in the nine-nation South American group with 13 points, 10 less than leaders Argentina and just inside the four direct qualifying berths for the 2014 finals in Brazil.
Chile, looking to recover from a run of four defeats including Friday's 1-0 loss to Peru in Lima, are just outside in sixth place with 12 points.
The team finishing fifth earns a play-off against an Asian qualifier for another berth.