The 30-year-old has suffered a string of injuries since helping his country finish third at the 2007 World Cup. His last Test was against England in June 2009.
The team will be captained by No 8 Juan Martin Fernandez Lobbe who takes over from Felipe Contepomi after the centre made himself unavailable for this tournament.
Prop Rodrigo Roncero, 35, will also play in his 50th Test for Argentina.
"The Springboks are a very powerful side and we will need to have control of the ball in order to have a good game," coach Santiago Phelan told reporters.
"We are aware of the Springboks' strengths. We need to be patient and find the moment in the game to strike.
"We have to find the spaces in order to generate momentum. It will be about space as they are physically very strong when you attack them one on one."
Wing Gonzalo Camacho said Argentina's inclusion in the southern hemisphere's premier rugby competition for the first time alongside South Africa, New Zealand and Australia was an important step for rugby in his country.
"We have been feeling the pressure heading into a huge game, the test will be huge. It is historic because SA is a world power, an elite side," said Camacho.
"We have to prove ourselves without losing the essence of our game."
The starting team at Newlands in Cape Town includes 14 players who play in Europe, with only flanker Julio Farias Cabello playing in Argentina. Twelve of the team took part in last year's World Cup in New Zealand.
Kick-off is at 17:10 on Saturday.
Teams:
South Africa:
TBA
Argentina:
15 Lucas Gonzalez Amorosino, 14 Gonzalo Camacho, 13 Marcelo Bosch, 12 Santiago Fernandez, 11 Horacio Agulla; 10 Juan Martin Hernandez, 9 Nicolas Vergallo, 8 Juan Martin Fernandez Lobbe (captain), 7 Alvaro Galindo, 6 Julio Farias Cabello, 5 Patricio Albacete, 4 Manuel Carizza, 3 Juan Figallo, 2 Eusebio Guinazu, 1 Rodrigo Roncero
Substitutes: 16 Bruno Postiglioni, 17 Marcos Ayerza, 18 Juan Pablo Orlandi, 19 Tomas Leonardi, 20 Leonardo Senatore, 21 Martin Landajo, 22 Martin Rodriguez
Coach: Santiago Phelan