Sportal.co.nz 16.Aug.2012Getty Images
The 27-year-old, who has made three substitute appearances for the Boks since making his Test debut in 2010, will pack down at number eight in place of the injured Pierre Spies, who requires surgery on his finger.
Springboks coach Heyneke Meyer said: "Keegan has been playing really well in (Investec) Super Rugby and he has put up his hand.
"It is a setback losing someone of Pierre's experience but I think that Keegan is the logical choice to replace Pierre. It is a step up and it is in his hands now to see if he can play at this level.
"What you lose in physicality with Keegan you gain with the X-factor he brings to the team."
South Africa's starting line-up shows six changes to the team who drew 14-14 with England in the third Test in June with Morne Steyn retained at first five-eighth despite criticism about his form.
South Africa: Kirchner, Mvovo, Villiers (captain), Frans Steyn, Habana, Morne Steyn, Hougaard, Daniel, Alberts, Coetzee, Bekker, Etzebeth, Jannie du Plessis, Bismarck du Plessis, Mtawarira.
Replacements: Strauss, Cilliers, van der Merwe, Potgieter, Pienaar, Lambie, Engelbrecht.