The 29-year-old will skipper the side for the 60th time in Brisbane after first captaining Australia as a 22-year-old in 2014, which made Hooper the third youngest Wallabies leader of all time.
Since making his International debut in 2012, Hooper has gone on to play 112 Tests for his country and will start in a settled back row alongside Lachlan Swinton at blindside flanker and No 8 Rob Valetini.
Fellow centurion James Slipper returns to the run-on side alongside Taniela Tupou, who earns a second start in 2021 at his home ground, with Folau Fainga’a finalising the front row at hooker.
Izack Rodda will continue his impressive return to the Test arena, again partnering Matt Philip in the second row at Suncorp Stadium.
Brumbies scrumhalf Nic White is the only change to the backline, earning his first start for the year and reigniting his partnership with last week’s match-winner Quade Cooper in the halves.
The damaging midfield duo of Samu Kerevi and Len Ikitau will get another chance to build their combination at inside and outside centre respectively.
Tom Banks has again been named at fullback with the 27-year-old having worn the No 15 jersey in every game for the Wallabies this year. He’s joined in the back three by Marika Koroibete and the in-form Andrew Kellaway.
Suncorp Stadium has proven a happy hunting ground for the Wallabies in recent years, with Australia having won eight straight Tests at the venue since 2016. A victory against the reigning world champions on Saturday night would also secure the Nelson Mandela Challenge Plate for the Wallabies.
Last weekend's victory over the world's number one side has helped Australia rise in the rankings, with the Wallabies now fifth.
Wallabies coach Dave Rennie said: “It’s an incredible milestone for Hoops on Saturday evening in Brisbane and it’s a testament to him as a person and a player.
“I’ve been so impressed with his leadership both on and off the field and his drive to be better every day.
“We were really proud of the effort from our men last Sunday and we’re well aware of the ferocity that a wounded Springboks outfit will bring to Suncorp Stadium.”
Wallabies team to play South Africa at Suncorp Stadium:
1. James Slipper (107 Tests)
2. Folau Fainga’a (18 Tests)
3. Taniela Tupou (32Tests)
4. Izack Rodda (27 Tests)
5. Matt Philip (16 Tests)
6. Lachlan Swinton (5 Tests)
7. Michael Hooper (captain, 112 Tests)
8. Rob Valetini (11 Tests)
9. Nic White (40 Tests)
10. Quade Cooper (71 Tests)
11. Marika Koroibete (40 Tests)
12. Samu Kerevi (35 Tests)
13. Len Ikitau (6 Tests)
14. Andrew Kellaway (6 Tests)
15. Tom Banks (18 Tests)
16. Feleti Kaitu’u (1 Test)
17. Angus Bell (9 Tests)
18. Tom Robertson (24 Tests)
19. Darcy Swain (6 Tests)
20. Pete Samu (12 Tests)
21. Tate McDermott (9 Tests)
22. Reece Hodge (50 Tests)
23. Jordan Petaia (11 Tests)