However, injury to Bismarck du Plessis just five minutes into last Saturday's win over Scotland meant Smit played the remainder of the Murrayfield match in the middle of the front row, a position he will again occupy in du Plessis' absence this time around.
Sharks prop Jannie du Plessis, brother of Bismarck, is named in the No3 shirt less than a week after joining up with the squad.
The other change to the starting XV sees Danie Rossouw promoted from the bench to the openside flank in place of Juan Smith who has not fully recovered from a knock to the head against Scotland.
Rossouw will win his 36th cap in London, while the final international of the World Champions' long season will be du Plessis' seventh in Springbok colours.
Rickie Januarie continues at scrum-half as Fourie du Preez continues to be unavailable due to a training ground injury he sustained in the build up to last week's 14-10 win.
Head coach Peter de Villiers makes two alterations to his seven replacements, with flanker Heinrich Brussow in line for a Test debut and hooker Chiliboy Ralepelle also promoted to the matchday squad.
Guthro Steenkamp drops out of the 22 after also picking up an injury in Scotland.
South Africa: Conrad Jantjes; JP Piteresen, Adrian Jacobs, Jean de Villiers, Bryan Habana; Ruan Pienaar, Ricky Junarie; Beast Mtawarira, John Smit (captain), Jannie du Plessis, Bakkies Botha, Victor Matfield, Schalk Burger, Danie Rossouw, Pierre Spies (18)
Replacements: Chiliboy Ralepelle, Brian Mujati, Andries Bekker, Ryan Kankowski, Heinrich Brussow, Frans Steyn, Jaque Fourie