Coach Jake White said: "Victor has played 57 Test matches, he led the Bulls to victory in the Super 14, and he took the reins when Smit was injured at the weekend."
White is also optimistic over the fitness of flanker Juan Smith, who left the field injured during the 22-19 defeat of Australia on Saturday.
"We have got to give him the benefit of the doubt because he is the first choice in that position and he is a lot better now than he was," he said.
Gary Botha will make his first start in Smit's place, while Os du Randt replaces Gurthro Steenkamp, who is also injured.
"It is amazing how it works out for you sometimes. We lost John, which is a massive blow, but at the same time Os is back, and he has 71 Test caps," added White.
"I am sure Gary will be pleased to have such an experienced guy alongside him."
Bismarck Du Plessis is the only uncapped player in the 22-man squad.
South Africa: P Montgomery; A Willemse, J Fourie, J de Villiers, JP Pietersen, B James, R Pienaar; O du Randt, G Botha, BJ Botha, B Botha, V Matfield (capt), S Burger, J Smith, P Spies.
Reserves: B Du Plessis, CJ Van der Linde, J Muller, D Rossouw, M Claassens, W Olivier, F Steyn.