Bakkies Botha has lost his battle to be fit for South Africa's opening World Cup game against Wales on Sunday.
The powerful lock has been troubled by an Achilles problem, and he is replaced by Danie Rossouw.
Rossouw's second-row partner will be 107-times-capped Victor Matfield, who features in the starting line-up despite suffering from a hamstring niggle earlier this week.
Coach Peter de Villiers has named the most experienced Springboks team in history, boasting a combined total of 815 caps. It surpasses the previous highest total of 810 against Australia in Durban last month.
There are five changes from South Africa's last game, an 18-5 Tri-Nations victory over New Zealand three weeks ago, with Rossouw, full-back Frans Steyn, prop Tendai Mtawarira, skipper John Smit and flanker Schalk Burger all recalled.
And De Villiers has gone for five forwards on the bench, including Ulster second row Johann Muller, who last played for the Boks in 2009 against the Lions. However, there was no place for Muller’s Ulster team-mate Ruan Pienaar in the 22-man squad.
There are 11 players in the starting XV who were part of South Africa's victorious 2007 World Cup squad, including wing Bryan Habana, who needs one try to break Joost van der Westhuizen's Springboks Test record of 38 touchdowns.
South Africa have won 23 of their previous 25 games against Wales.
Team: F Steyn; J P Pietersen, J Fourie, J de Villiers, B Habana; M Steyn, F du Preez; T Mtawarira, J Smit (capt), J du Plessis, D Rossouw, V Matfield, H Brussow, S Burger, P Spies. Replacements: B du Plessis, G Steenkamp, C J van der Linde, J Muller, W Alberts, F Hougaard, B James.