There are four personnel changes from the starting XV which defeated Australia last Sunday with two each in the forwards and backs, and two on the replacements bench from the Wallabies fixture, along with a positional change in the pack.
Stuart Hogg leads the team from full-back winning his 87th cap, which draws him level with lock Scott Murray in fourth position on the all-time Scotland capped list.
Leicester Tigers centre Matt Scott earns his first Scotland start since June 2017, when he played against Italy in Singapore in Gregor Townsend's first match as Head Coach.
Scott comes in for his 40th Scotland cap and partners Gloucester Rugby's Chris Harris, who played South Africa for the British & Irish Lions this summer.
Glasgow Warrior's Rufus McLean starts on the wing after his double try-scoring debut against Tonga earlier in the 2021 Autumn Nations Series, with Worcester Warriors and Lion Duhan van der Merwe completing the back three.
In the pack Edinburgh Rugby's Nick Haining comes into the starting back-row on the blindside flank as club-mate and Vice-Captain Jamie Ritchie moves to the openside.
Hamish Watson, himself a Lions tourist this summer, is named in the replacements.
There is a return to the front-row for Edinburgh Rugby's Stuart McInally at hooker and he packs down with Lion Zander Fagerson and Edinburgh Rugby's Pierre Schoeman, who earns his third start at loosehead prop.
Edinburgh Rugby's Grant Gilchrist and Exeter's Sam Skinner continue their second-row partnership following their role in the win over the Wallabies on Sunday.
Townsend has added experience to the replacements with Edinburgh Rugby's Blair Kinghorn providing cover across the backs alongside Glasgow Warriors scrum-half George Horne and Gloucester Rugby's Adam Hastings.
Scotland Head Coach Gregor Townsend said: "Sunday's result against Australia was another positive step in the evolution of this team, but there is more to come from this group. And we'll have to raise our level of performance on Saturday against the world champions.
"We know what to expect from the Springboks in how they play and the physicality they will bring across the team. We have therefore selected a side that we believe can both meet that challenge and give us the platform to impose our game on the opposition. It should be a full-blooded contest and will require an intensity and focus across our 23-man squad for the full 80 minutes.
"As a playing and coaching group we took a huge amount of energy from the crowd at BT Murrayfield through their outstanding support against Australia. We can't wait to get back out in front of our people again this weekend."
15 Stuart Hogg - Exeter - (Captain)
1 Pierre Schoeman - Edinburgh Rugby
2 Stuart McInally - Edinburgh Rugby
3 Zander Fagerson - Glasgow Warriors
4 Sam Skinner - Exeter
5 Grant Gilchrist - Edinburgh Rugby
6 Nick Haining - Edinburgh Rugby
7 Jamie Ritchie - Edinburgh Rugby - (Vice-Captain)
8 Matt Fagerson - Glasgow Warriors
16 Ewan Ashman - Sale Sharks
17 Jamie Bhatti - Glasgow Warriors
18 Oli Kebble - Glasgow Warriors
19 Jamie Hodgson - Edinburgh Rugby
20 Hamish Watson - Edinburgh Rugby
21 George Horne - Glasgow Warriors
22 Adam Hastings - Gloucester Rugby
23 Blair Kinghorn - Edinburgh Rugby