Argentina escaped Group A with five points, finishing in second place.
The host nation could only manage one goal from their first two games in the competition, but they came alive in the last game against Costa Rica, winning 3-0.
Striker Sergio Aguero is the leading scorer in the tournament with three goals, including a brace against Costa Rica.
This will be Argentina's second game in Santa Fe in the Copa America. They drew 0-0 against Colombia in their first appearance in the province.
The winner of the contest will face the victor of Colombia and Peru in the semi-finals in La Plata on Tuesday.
Uruguay finished second in Group C with five points, two behind winners Chile.
The leading scorer on the team in the tournament is not Forlan, Suarez or Cavani; it is defender Alvaro Pereira, who has two goals.
A win would clinch Uruguay's fifth straight appearance in the semi-finals.
The last meeting that took place between the two sides was in October 2009 when a Mario Bolatti goal six minutes from time clinched Argentina's qualification to the World Cup in South Africa.
Cavani will not play as he is still recuperating from a knee injury suffered against Chile in their second game. The striker did not play in the 1-0 victory over Mexico.
PROBABLE LINE-UPS
Argentina:
Romero; Zabaleta, Burdisso, G. Milito, Zanetti; Gago, Mascherano; Aguero, Messi, Di Maria; Higuain.
No changes for Argentina as Sergio Batista calls the same line-up that earned a 3-0 victory against Costa Rica last time out.
Uruguay:
Muslera; M. Pereira, Lugano, Victorino, Caceres, A. Pereira; Gonzalez, Perez, Rios; Forlan, Suarez.
Oscar Tabarez will look to Diego Forlan and Luis Suarez to find the net against their neighbors as they are shorthanded with the absence of Edinson Cavani, who is still recovering from injury.
Prediction
Anything less than winning the tournament would be a failure for Sergio Batista's men. Now in the quarter-finals, Argentina should get a step closer to their dream with the potent attack of Lionel Messi, Gonzalo Higuain, Sergio Aguero and Angel Di Maria. If they can create chances at the same pace they did against Costa Rica, the host nation should be able to put a few away and advance past Uruguay.
Editor's Prediction
Argentina 2-1 Uruguay 
