It is a much changed selection from the team that failed to impress in a 42-24 victory over the touring Italians in Pretoria last week.
Le Roux becomes the eighth player to reach 100 caps for the Springboks and makes up a back three that also includes wings Makazole Mapimpi and Edwill van der Merwe.
"Willie has been a stalwart for us in the last few years after making his debut against Italy in Durban in 2013, and he's a fantastic playmaker, so we are thrilled to see him achieve this incredible feat," Erasmus said.
There is a return from injury for Pieter-Steph du Toit alongside fellow flanker Marco van Staden, with Jasper Wiese keeping his place at number eight.
Cobus Wiese, brother of No.8 Jasper, is one of three uncapped players on the bench along with prop Asenathi Ntlabakanye and utility back Ethan Hooker.
SOUTH AFRICA (to play Italy):
Le Roux, Van der Merwe, Moodie, Esterhuizen, Mapimpi, Libbok, Williams, J Wiese, P-S Du Toit, Van Staden, Nortje, Moerat, Louw, Marx, T du Toit
Replacements: Wessels, Nche, Ntlabakanye, Cs Wiese, Roos, Reinach, Feinberg-Mngomezulu, Hooker
