Liam Williams, who won his 50th cap against Tonga last weekend, comes into the starting XV, replacing Leigh Halfpenny at full-back who is ruled out with concussion.
Warren Gatland made 14 changes for the victory over Tonga last weekend but has reverted back to the side that defeated the Wallabies.
Williams lines up in the backline alongside fellow British & Irish Lion George North and Josh Adams.
Scarlets duo Hadleigh Parkes and Jonathan Davies are named in the midfield with Gareth Davies and Gareth Anscombe continuing their partnership at half-back.
In the pack Nicky Smith, Ken Owens and Tomas Francis are again named in the front-row with Adam Beard, unbeaten in a Wales jersey, lining up alongside captain Alun Wyn Jones.
Dan Lydiate, Justin Tipuric and Ross Moriarty pack down in the back-row for a third time together this autumn.
“We have rewarded the team that faced Australia with another start this weekend,” said Wales head coach Warren Gatland.
“Leigh (Halfpenny) misses out with concussion but it’s a great opportunity for Liam (Williams) at full-back.
“We are really pleased with how the bench has gone in the first three games so we will be looking for that impact again on Saturday.
“There were a lot of tough selection calls, but that is what we want. The team that played last week was hugely impressive and there are some disappointed boys who miss out.
“We want to end the campaign with a big performance against a very good South African side.”
Elliot Dee, Rob Evans and Dillon Lewis provide the front-row cover on the bench with Cory Hill and Ellis Jenkins completing the forwards. Tomos Williams, Dan Biggar and Owen Watkin provide the backline cover.
WALES SQUAD TO PLAY SOUTH AFRICA (Saturday November 24 KO 17.20)
15. Liam Williams (50 Caps)
14. George North (78 Caps)
13. Jonathan Davies (67 Caps)
12. Hadleigh Parkes (10 Caps)
11. Josh Adams (5 Caps)
10. Gareth Anscombe (20 Caps)
9. Gareth Davies (35 Caps);
1. Nicky Smith (23 Caps)
2. Ken Owens (59 Caps)
3. Tomas Francis (35 Caps)
4. Adam Beard (7 Caps)
5. Alun Wyn Jones (119 Caps) (CAPT)
6. Dan Lydiate (64 Caps)
7. Justin Tipuric (59 Caps)
8. Ross Moriarty (25 Caps)
REPLACEMENTS:
16. Elliot Dee (12 Caps)
17. Rob Evans (30 Caps)
18. Dillon Lewis (7 Caps)
19. Cory Hill (21 Caps)
20. Ellis Jenkins (10 Caps)
21. Tomos Williams (5 Caps)
22. Dan Biggar (64 Caps)
23. Owen Watkin (7 Caps)
Released players:
The following players have been released from the national squad back to their respective regions:
Seb Davies (Cardiff Blues)
Jarrod Evans (Cardiff Blues)
Tyler Morgan (Dragons)
Hallam Amos (Dragons)
Luke Morgan (Ospreys)
