Damian de Allende will make his Springbok debut next to returning national captain Jean de Villiers against Argentina at Loftus Versfeld in Pretoria.
De Villiers is one of three returning Springboks who played no part in the June Tests because of injury. The others are Frans Malherbe and Eben Etzebeth, who have both been selected on the bench.
Junior Springbok captain Handré Pollard will get his second Test cap when he lines up between the experienced De Villiers and Ruan Pienaar, while Willem Alberts and Tendai Mtawarira are also back after missing the Scotland Test because of injuries.
At lock, Lood de Jager will have to fill the considerable boots of the injured Victor Matfield, but he'll have the experienced Bakkies Botha next to him.
"It's great to welcome back Jean, Willem, 'Beast', Eben and Frans, but I'm also very excited to see what Damian can do after he missed out on making his debut in June because of an injury," said Springbok coach Heyneke Meyer.
"Jean and Damian have played together before, albeit not this way around. But Damian has experience of playing outside centre from his junior days and he got his break at inside centre when he had to step up in Jean's place.
"Handré also deserved another opportunity and it will be good to see how he combines with Jean and Damian.
"Lood has improved a lot over the last couple of months and although it's a big ask for him to fill the void left by Victor, I know he has the goods to deliver. He will be well-supported by Duane Vermeulen in the line-outs though."
Meyer moved Jan Serfontein, who had a very good series in June, to the bench as injury cover, with De Villiers and De Allende both returning from injuries, while Morne Steyn will provide back-up at fly-half and full-back.
"Jan was one of our best players in June, but Jean is our captain and was always going to return once he was fit again," said Meyer.
"We're up against a formidable opponent on Saturday and we can't take any chances or make experiments. The players know they have to be switched on mentally and physically, otherwise it could become a long afternoon at Loftus."
Pat Lambie will return to Durban on Wednesday to play for the Sharks in the Currie Cup on Friday, when they host the Steval Pumas.
"Pat missed four months of Super Rugby and although he made his return towards the end of the competition, it was felt that he could do with game time this weekend before we leave for Argentina and we'd like to thank the Sharks for agreeing to give him a run."
South Africa: 15 Willie le Roux, 14 Cornal Hendricks, 13 Damian de Allende, 12 Jean de Villiers (c), 11 Bryan Habana, 10 Handré Pollard, 9 Ruan Pienaar, 8 Duane Vermeulen, 7 Willem Alberts, 6 Francois Louw, 5 Lood de Jager, 4 Bakkies Botha, 3 Jannie du Plessis, 2 Bismarck du Plessis, 1 Tenda Mtawarira
Replacements: 16 Adriaan Strauss, 17 Trevor Nyakane, 18 Frans Malherbe, 19 Eben Etzebeth, 20 Marcell Coetzee, 21 Francois Hougaard, 22 Morné Steyn, 23 Jan Serfontein
Date: Saturday, August 16
Venue: Loftus Versfeld, Pretoria
Kickoff: 16:05 (local, 14:05 GMT)
Referee: John Lacey (Ireland)
Assistant Referees: Steve Walsh (Australia), Marius Mitrea (Italy)
TMO: Simon McDowell (Ireland)