Quade Cooper will make his long-awaited return to the Wallabies side, named at flyhalf for Sunday's clash against the Springboks at CBUS Super Stadium.
Cooper has not featured on the International stage since 2017, set to line up alongside Tate McDermott in the third round of The Rugby Championship.
"We’re thrilled for Quade that he’s earned another opportunity to pull on the gold jersey for his country," coach Dave Rennie said
“He’s had a really positive impact since joining the group, put pressure on us as selectors and he’s excited to get out there and perform on Sunday night."
In further changes, Angus Bell will get his first start of the year, joining Folau Fainga'a and Allan Alaalatoa in the front-row.
In a match full of milestones, Alaalatoa will bring up his 50th cap for the Wallabies along with Reece Hodge, who will appear off the bench.
Izack Rodda comes into the starting side alongside Matt Philip to complete the tight-five after making his return last week via the bench.
Aside from Cooper, the backline is unchanged, with Samu Kerevi and Len Ikitau retaining their spots in the centre despite Hunter Paisami returning to camp.
Western Force hooker Feleti Kaitu'u and Rebels back-rower Rob Leota are in line for their debut off the bench.
The match will also see captain Michael Hooper equal George Gregan’s record for most Tests as Wallabies captain when he leads the side out for the 59th time.
He will also go into outright fifth for appearances ahead of George Smith with his 112th cap.
"The match is also a huge occasion for our leader Michael Hooper. He’s been in phenomenal form and to equal George Gregan’s record as the most Tests as captain of Australia is a testament to his leadership and resilience," Rennie added.
“We also can’t overlook Allan and Reece who will bring up 50 Tests for their country, another outstanding achievement for two ultimate professionals who leave it all on the field every time they wear the jersey.”
Wallabies team to play South Africa at Cbus Super Stadium, Gold Coast on Sunday 12 September, 8:05pm AEST
1. Angus Bell (8 Tests)
2. Folau Fainga’a (17 Tests)
3. Allan Alaalatoa (49 Tests)
4. Izack Rodda (26 Tests)
5. Matt Philip (15 Tests)
6. Lachlan Swinton (4 Tests)
7. Michael Hooper (c) (111 Tests)
8. Rob Valetini (10 Tests)
9. Tate McDermott (8 Tests)
10. Quade Cooper (70 Tests)
11. Marika Koroibete (39 Tests)
12. Samu Kerevi (34 Tests)
13. Len Ikitau (5 Tests)
14. Andrew Kellaway (5 Tests)
15. Tom Banks (17 Tests)
16. Feleti Kaitu’u*
17. James Slipper (106 Tests)
18. Taniela Tupou (31 Tests)
19. Rob Leota*
20. Pete Samu (11 Tests)
21. Nic White (38 Tests)
22. Reece Hodge (49 Tests)
23. Jordan Petaia (10 Tests)