The alterations see Finn Russell named to start at fly-half after his recovery from a calf injury, whilst Zander Fagerson and Gregor Brown are promoted to the starting XV after coming off the bench in last weekend's victory over Argentina.
Fagerson lines up at tighthead after a tour-ending injury to Elliot Millar Mills in Cordoba last Saturday, joining Pierre Schoeman - a try-scorer on his 50th cap for Scotland last time out - and Ewan Ashman in the front row.
Scott Cummings continues in the second row after also touching down for a try on his 50th cap, with Brown coming into the line-up after crossing for his first score in Scotland colours last weekend.
The back row is unchanged, meaning Matt Fagerson and Rory Darge - the latter having led the team with 24 tackles against Los Pumas - start either side of Jack Dempsey to form the loose forward trio.
Ben White partners Russell in the half-backs, with the scrumhalf having been pivotal in controlling proceedings in Cordoba last Saturday.
Rory Hutchinson retains his place at outside centre after an impressive, try-scoring performance in the number 13 jersey last weekend, once again forming a midfield partnership with captain Sione Tuipulotu ahead of the clash at Loftus Versfeld.
An all-Glasgow Warriors back-three sees Kyle Steyn and Jamie Dobie selected on the wings, as Kyle Rowe rounds out the starting XV by lining up at fullback.
A six-two split of forwards and backs on the replacements bench sees Rory Sutherland in line to win his 50th cap for Scotland should he come onto the field this weekend, the loose-head prop set to reach the milestone in the country in which he toured as a British & Irish Lion in 2021.
Gregor Hiddleston is retained amongst the replacements after a memorable debut in last weekend's victory over Argentina, with Alex Samuel also retained from last weekend’s cohort of replacements.
Tom Jordan rotates to the bench after starting last time out, whilst Will Hurd, Josh Bayliss, Magnus Bradbury and Stafford McDowall are all set for their first appearances of the 2026 Nations Championship after being named in the matchday 23.
The match will mark Scotland's first clash with the double world champions on South African soil since 2014.
Scotland - 15 Kyle Rowe, 14 Kyle Steyn, 13 Rory Hutchinson, 12 Sione Tuipulotu (c), 11 Jamie Dobie, 10 Finn Russell, 9 Ben White, 8 Jack Dempsey, 7 Rory Darge, 6 Matt Fagerson, 5 Scott Cummings, 4 Gregor Brown, 3 Zander Fagerson, 2 Ewan Ashman, 1 Pierre Schoeman.
Replacements: 16 Gregor Hiddleston, 17 Rory Sutherland, 18 Will Hurd, 19 Alex Samuel, 20 Josh Bayliss, 21 Magnus Bradbury, 22 Tom Jordan, 23 Stafford McDowall.