The Springboks lost 19-16 to Ireland in Dublin at the weekend, a below-par performance that has seen coach Jacques Nienaber make five changes to his starting lineup.
Le Roux comes into the side in the No.15 jersey, with Cheslin Kolbe moving to the wing in the place of Makazole Mapimpi, and De Klerk taking over from Jaden Hendrikse.
Tighthead prop Frans Malherbe comes into a new-look front row alongside Ox Nche and hooker Bongi Mbonambi, while Franco Mostert takes over at lock from the injured Lood de Jager.
"We opted to make a few tactical personnel changes for the challenge that we expect France to pose," Nienaber said in a media release from South African Rugby on Tuesday.
"We know what each of the players in this squad can do, and we thought these combinations fit this specific game."
The Boks have included uncapped flyhalf Manie Libbok on the bench after they struggled with their goal-kicking in Dublin in the absence of injured Handre Pollard.
Damian Willemse and Kolbe shared the duties with limited success.
Nienaber has also added an extra back on the bench for a 5-3 split, with scrumhalf Cobus Reinach and Mapimpi the others that could potentially be introduced.
"A guy like Cobus will bring a different dimension to our attack, and it a bonus that he knows the conditions in France and has played with some of their players," Nienaber said.
"Manie has showed his big match temperament in the United Rugby Championship and he has been training well since joining the team, so if he gets a run, it will be a great occasion to make his Test debut."
Nienaber sees the fixture as perfect preparation for the Rugby World Cup next year, where the Boks could find themselves facing hosts France in the quarter-finals.
"Facing France on their home patch at what we expect will be a full stadium is great preparation for next year, as the players will experience first-hand what they are in for.
"We will also be playing at this stadium during the World Cup, so this match will be good for us in many ways."
South Africa: Willie le Roux, Cheslin Kolbe, Jesse Kriel, Damian de Allende, Kurt-Lee Arendse, Damian Willemse, Faf de Klerk, Jasper Wiese, Pieter-Steph du Toit, Siya Kolisi (capt), Franco Mostert, Eben Etzebeth, Frans Malherbe, Bongi Mbonambi, Ox Nche. Replacements: Malcolm Marx, Steven Kitshoff, Vincent Koch, Marvin Orie, Kwagga Smith, Cobus Reinach, Manie Libbok, Makazole Mapimpi.
