Brits replaces the suspended Bismarck du Plessis to make his first appearance of the campaign, with Spies also makingh his bow in this year's competition in place of Joe van Niekerk.
Jantes returns to the No15 jersey having starting the first of the back-to-back matches against the All Blacks but then been replaced by Percy Montgomery for the historic win in Dunedin. Montgomery misses out on selection altogether for teh clash with the Wallabies.
The other enforced alteration involves the mercurial Steyn, who takes over from the injured Adrian Jacobs in midfield.
With Brits stepping up to the starting XV, newcomer Adriaan Strauss, who joined the squad on Tuesday as back-up hooker, has been included as one of the replacements.
De Villiers has decided to name five forwrads and just two backs among his seven replacements, with Ryan Kankowski also elevated to the matchday squad
This will be the fourth match between Australia and South Africa at the Subiaco Oval in Perth, following on from 1998, 2001, 2004 and 2005. South Africa have won in Perth twice previously - 14-13 in 1998 and 22-19 three years ago.
South Africa (vs Australia, Saturday, July 19, kick off 11.05am BST)
15. Conrad Jantjes
14. JP Pietersen
13. Francois Steyn
12. Jean de Villiers
11. Bryan Habana
10. Butch James
9. Enrico Januarie
8. Pierre Spies
7. Juan Smith
6. Schalk Burger
5. Victor Matfield (c)
4. Bakkies Botha
3. CJ van der Linde
2. Schalk Britsv
1. Gurthro Steenkamp
Replacements
16. Adriaan Strauss
17. Tendai Mtawarira
18. Brian Mujati
19. Andries Bekker
20. Ryan Kankowski
21. Ruan Pienaar
22. Peter Grant
Supporters can watch the Springboks continue their build up to the 2009 Lions tour live on Sky Sports on Saturday morning.
