Uruguay were held to a 1-1 draw in their opening game against Peru, with Luis Suarez's 45th minute strike cancelling out Paolo Guerrero's effort.
La Celeste lost their previous encounter against Claudio Borghi's men, with Uruguay going down 2-0 and also had Walter Gargano sent off.
Diego Forlan is just two goals shy of matching Uruguay's goalscoring record, currently held by Hector Scarone with 31.
Uruguay prevailed the last time both sides met in the Copa America, winning 5-3 on penalties in the 1999 semi-final en route to losing 3-0 to Brazil in the final.
The two sides have an identical record against each other, with both Uruguay and Chile winning twice each, and drawing three of their seven games.
Chile opened their tournament with a come-from-behind 2-1 victory against Mexico on Monday.
Although La Roja have failed to progress beyond the first round on four of the last eight encounters, they will do so if they secure three points against Uruguay.
Claudio Borghi's side are unbeaten in nine games, only losing once since bowing out of the World Cup in the second round.
PROBABLE LINE-UPS
Uruguay:
Muslera; Pereira, Lugano, Coates, Caceres; Perez, Arevalo, Alvaro Pereira; Cavani, Forlan, Suarez
Coach Oscar Tabarez is set to make two changes from the side that opened their tournament with a 1-1 draw against Peru. Sebastien Coates, who only made his international debut last month, will step in for Mauricio Victorino in defence. Nicolas Lodeiro will also make way for Alvaro Pereira in Mendoza. Diego Godin is still struggling with a fever, and remains doubtful.
Chile:
Bravo; Jara, Ponce, Contreras; Beausejour, Medel, Isla, Vidal, Fernandez; Sanchez, Suazo.
Claudio Borghi is sweating on the fitness of Matias Fernandez after the Sporting man went off injured in the 2-1 win over Mexico on Monday. Otherwise, there are no pressing concerns for La Roja to mull over. Chile will move into the last eight if they defeat last year's World Cup semi-finalists.
Prediction
Both sides posess a considerable attacking arsenal, yet with Uruguay's stuttering display, it'll be hard for them to convincingly overcome a fabulously talented Chilean side. Nevertheless, the attacking trident of La Celeste are among the finest in world football, and should they perform to their undoubted potential, a narrow win could well be on the cards for Oscar Tabarez's men.
Uruguay 2-1 Chile 
