Jacques Potgieter will make his Springbok debut as one of three changes for the final Test with England.
The open-side flanker replaces the injured Willem Albertz in Port Elizabeth on Saturday.
Gio Aplon comes in at full-back for Pat Lambie and Wynand Olivier takes over at inside centre for Frans Steyn, who is getting married this weekend.
South Africa go into the game holding an unassailable 2-0 lead in the three Test series.
Head coach Heyneke Meyer is excited by the return to the South Africa line-up of Aplon, who has 16 caps.
"He can do something magic from the back. He runs great lines, has unbelievable feet and brings an X-factor," said the coach.
"He has looked good in training and there is no pecking order and if he shows and proves that he is the best full-back, then there is no reason why he can't play going forward."
Meyer also announced series captain Jean de Villiers will lead the team for the rest of the season.
"Jean has been unbelievable as captain and has matched my expectations," said Meyer.
"We want to plan for the rest of the year. It is always important to have a special leader to gel the team and there is a lot of respect for him from the players.
"It was very easy to make him captain. I have worked with a lot of good captains and he is right up there."
South Africa: G Aplon; J P Pietersen, J de Villiers (capt), W Olivier, B Habana; M Steyn, D Hougaard; T Mtawarira, B du Plessis, J du Plessis, E Etzebeth, J Kruger, M Coetzee, J Potgieter, P Spies.
Replacements: A Strauss, W Kruger, F van der Merwe, R Kankowski, R Pienaar, B Basson, E Jantjies.