Handre Pollard will start at fly-half after South Africa coach Allister Coetzee made four changes to his side for Saturday's international Test against France in Paris.
Duane Vermeulen comes in at No.8 and Wilco Louw at tighthead prop in two forced switches due to injuries to Pieter-Steph du Toit and Coenie Oosthuizen.
Elton Jantjies drops to the bench after starting at outside half in last week's record 38-3 defeat to Ireland, as does centre Damian de Allende, with Francois Venter promoted to the starting XV for the 1945GMT kick-off.
Coetzee said Pollard's inclusion was more a case of rotation than of dropping Jantjies.
"Handre Pollard, his inclusion this week, I think it's the right time," said the coach.
"He's looking sharp in training. I'm pleased with Elton's development and his effort this year.
"He's started off 10 tests but it's time to give Handre Pollard an opportunity as well.
"It's great to have both your tens out there in northern hemisphere conditions being able to manage games up here."
Toulon back row Vermeulen was only called into the squad after prop Oosthuizen was diagnosed with knee ligament damage sustained in the opening minutes against Ireland that will require surgery.
Loose forward Du Toit suffered concussion and will miss the match against France, meaning Coetzee needed an experienced line-out operator.
"It's a simple selection for me in a sense. Obviously it's a logical one after losing Pieter-Steph du Toit, who's a good lineout exponent.
"We do need another lineout guy to replace Pieter-Steph du Toit in that option and Duane Vermeulen is really suiting that role perfectly.
"Also, at least there's a specialist number eight in the team and he brings a lot of leadership and will support (captain) Eben (Etzebeth) tremendously."
Louw played almost the entire match against Ireland in only his second appearance for the Boks after replacing Oosthuizen and now gets the chance to start, with Trevor Nyakane coming onto the bench.
With Jan Serfontein ruled out of the Boks' European Tour following his move from Bulls to French Top 14 outfit Montpellier, Coetzee was forced into a change of midfield combination.
- 'We need a bit extra' -
Serfontein had played alongside outside centre Jesse Kriel in eight of nine Tests in 2017 before the Dublin debacle last week, when De Allende was given the nod.
"Damian, ball in hand he's carried well but what we lost in Jan is a bit extra than just carrying the ball, and I think Francois (Venter) has played consistently well for the Cheetahs this season," said Coetzee.
"He's that industrious, hardworking centre -- that's what we're actually looking for from him and his contributions not just in one department but in all departments."
Like South Africa, France come into this game off a heavy loss, 38-18 to New Zealand last weekend, and Coetzee believes both sides will be desperate to make amends.
The key for him, is who manages to get over the gain line.
"We've had a good look at the French and they're a very, very good side," he said.
"We've got to make sure of the collisions -- that's the first battle, the gain line and then set piece.
"So that's what the game will be about, that dominance that should be earned on the gain line."
South Africa take a five-match winning run over the French into this game at the Stade de France having not lost to their hosts since 2009.
France: 15 Nans Ducuing, 14 Teddy Thomas, 13 Geoffrey Doumayrou, 12 Mathieu Bastareaud, 11 Yoann Huget, 10 Anthony Belleau, 9 Antoine Dupont, 8 Louis Picamoles, 7 Kevin Gourdon, 6 Judicael Cancoriet, 5 Paul Gabrillagues, 4 Sébastien Vahaamahina, 3 Rabah Slimani, 2 Guilhem Guirado (captain), 1 Jefferson Poirot.
Replacements: 16 Clement Maynadier, 17 Sébastien Taofifénua, 18 Daniel Kotze, 19 Paul Jedrasiak, 20 Anthony Jelonch, 21 Baptiste Serin, 22 Francois Trinh-Duc, 23 Damian Penaud.
South Africa: 15 Andries Coetzee, 14 Dillyn Leyds, 13 Jesse Kriel, 12 Francois Venter, 11 Courtnall Skosan, 10 Handré Pollard, 9 Ross Cronje, 8 Duane Vermeulen, 7 Siya Kolisi, 6 Francois Louw, 5 Lodewyk de Jager, 4 Eben Etzebeth (captain), 3 Wilco Louw, 2 Malcolm Marx, 1 Tendai Mtawarira.
Replacements: 16 Mbongeni Mbonambi, 17 Steven Kitshoff, 18 Trevor Nyakane, 19 Franco Mostert, 20 Daniel du Preez, 21 Rudy Paige, 22 Elton Jantjies, 23 Damian de Allende.
Date: Saturday, November 18
Kick-off: 20.45 (19.45 GMT; 21.45 SA time}
Venue: Stade de France, Paris
Expected weather conditions: Partly cloudy with a high of 10°C, dropping to 6°C, as winter gets closer.
Referee: Nigel Owens (Wales)
Assistant referees: Wayne Barnes (England), Tom Foley (England)
TMO: Rowan Kitt (England)