Rohan Janse van Rensburg, Jamba Ulengo and Uzair Cassiem will make their Springbok debuts against Wales on Saturday.
Janse van Rensburg, who takes over from Damian de Allende in a rotational switch, and winger Ulengo, who is in for Bryan Habana, are part of a reshuffled backline announced by Springbok coach Allister Coetzee on Thursday.
Both Janse van Rensburg and Ulengo played for South Africa in the international match against the Barbarians three weeks ago at Wembley Stadium in London, but will now become officially capped Springboks.
Cassiem, who didn’t feature against the Baabaas, will also get his Test debut after Willem Alberts was ruled out because of a neck niggle.
A new-look backline also sees the return of Faf de Klerk (scrum-half) and Elton Jantjies (fly-half) as halfback combination, while there is a further change at full-back, with Johan Goosen named to start in the number 15 jersey.
In the other change upfront, Lourens Adriaanse comes in at tighthead in place of Vincent Koch, which means that 14 players who will be based in South Africa for Vodacom Super Rugby in 2017 will start against Wales, with a further seven on the bench.
Coetzee said the revamped side was picked as result of a combination of factors. Apart from rotational changes and injuries, some of the selections were made with the building process towards 2019 in mind. The total amount of caps amongst the backs are 40, the lowest amount since 1994.
"We have a less experienced team, but I want to see some energy and an improved performance. Our selection is also keeping in mind of the process and necessity to build towards 2019," said Coetzee.
"Uzair was impressive during our domestic competitions and he was man of the match in the Currie Cup final. He made a good impression during the build-up to the Barbarians match and has continued to work hard on this tour since re-joining us.
"Jamba, Uzair and Rohan are examples of players who have forced their way into the squad through consistently performing well on the domestic scene and during training on tour, and now they are getting their opportunities to play for the Boks. Even though Damian played well against England and Italy we felt Rohan deserved an opportunity."
Regarding the change in the front row, the coach added: "Lourens played well whenever he was selected and he too deserves his opportunity."
South Africa: 15 Johan Goosen‚ 14 Ruan Combrinck‚ 13 Francois Venter‚ 12 Rohan Janse van Rensburg‚ 11 Jamba Ulengo‚ 10 Elton Jantjies‚ 9 Faf de Klerk‚ 8 Warren Whiteley‚ 7 Uzair Cassiem‚ 6 Nizaam Carr‚ 5 Lood de Jager‚ 4 Pieter-Steph du Toit‚ 3 Lourens Adriaanse‚ 2 Adriaan Strauss (c)‚ 1 Tendai Mtawarira
Replacements: 16 Malcolm Marx‚ 17 Steven Kitshoff‚ 18 Trevor Nyakane‚ 19 Franco Mostert‚ 20 Jean-Luc du Preez‚ 21 Piet van Zyl‚ 22 Pat Lambie‚ 23 Lionel Mapoe
Date: Saturday, November 26
Venue: Principality Stadium
Time: 17:30 local (19:30 GMT)
Referee: Romain Poite (France)
Assistant Referees: Greg Garner (England), Tom Foley (England)
TMO: Graham Hughes (England)