Jesse Kriel takes over at outside centre alongside Damian de Allende, with Lukhanyo Am slipping to the bench as part of a 5-3 split between forwards and backs that is a move away from The Boks’ usual 6-2.
Manie Libbok is restored at fly half alongside number nine Grant Williams, who makes his first international start.
Duane Vermeulen returns at number eight and will captain the side. He makes up the back row alongside Pieter-Steph du Toit and Marco van Staden.
The lock pairing will be old school friends Marvin Orie and Eben Etzebeth, with Marx to start at hooker and props Frans Malherbe and Steven Kitshoff either side of him.
"This is a quality team that will offer us the skills we need against Argentina," Nienaber said in a media release from South African Rugby.
"It also contains a good balance of experience and youth, which is vital as we build toward the Rugby World Cup," he added. "We're pleased with the way we've managed that process up to now."
South Africa still can win the Rugby Championship but will likely need a bonus-point win over Argentina and hope New Zealand get nothing from their fixture against Australia in Melbourne.