A calf injury rules out Jeronimo de la Fuente and fellow centre Marias Moroni, scrum-half Tomas Cubelli, lock Guido Petti and flanker Javier Ortego Desio have been demoted.
Cubelli from Australian Super Rugby outfit ACT Brumbies -- the only non Argentina-based player in the matchday 23 -- Petti and Desio are among the replacements named by coach Daniel Hourcade.
Into the Los Pumas starting line-up come centres Matias Orlando and veteran Juan Martin Hernandez, scrum-half Martin Landajo, lock Matias Alemanno and flanker Juan Manuel Leguizamon.
France triumphed 27-0 after a 30-19 loss in the first of two away internationals while Argentina overcame Italy 30-24 at home in another June Test.
Hooker Agustin Creevy skippers the team in his 50th appearance for the 2015 Rugby World Cup semi-finalists.
A policy of choosing only home-based players -- with the exception of Cubelli -- means no place for winger Juan Imhoff from French Top 14 champions Racing 92.
He scored three tries in the corresponding fixture last season which Argentina won 37-25 in Durban, their only victory over the Springboks in 22 meetings.
The four-nation Rugby Championship kicks off Saturday in Sydney with a clash between title-holders Australia and world champions New Zealand.
Team (15-1)
Joaquin Tuculet; Santiago Cordero, Matias Orlando, Juan Martin Hernandez, Manuel Montero; Nicolas Sanchez, Martín Landajo; Facundo Isa, Juan Manuel Leguizamon, Pablo Matera; Tomas Lavanini, Matías Alemanno; Ramiro Herrera, Agustín Creevy (capt), Nahuel Tetaz Chaparro
Replacements: Julian Montoya, Felipe Arregui, Enrique Pieretto, Guido Petti, Javier Ortega Desio, Tomas Cubelli, Santiago Gonzalez Iglesias, Ramiro Moyano
Coach: Daniel Hourcade