Prop Taniela Tupou will earn his first Test start when he runs out at Nelson Mandela Bay Stadium after six appearances off the bench to open his International career.
Tupou will bookend the scrum alongside Scott Sio who is set to notch his 50th Test cap.
Captain Michael Hooper returns to the side after being a late scratching from Australia’s 19-23 defeat to Argentina a fortnight ago and he’s joined by Ned Hanigan in the backrow.
In the other change, Adam Coleman re-gains his spot at lock after coming off the bench against Argentina on the Gold Coast.
Australia haven’t tasted victory in South Africa since 2011 but did earn a draw in the Republic last year, when both sides fought out a 27-all stalemate in Bloemfontein.
Saturday’s clash will be the first meeting between the two sides in Port Elizabeth since 1963, when South Africa won 22-6 to level the four-match Test series.
Wallabies team to play South Africa at Nelson Mandela Bay Stadium, Port Elizabeth on Saturday 29 September
Rugby Championship Fixtures and Results
Wallabies 13 v New Zealand 38 at ANZ Stadium, Sydney, Saturday 18 August
New Zealand 40 v Wallabies 12 at Eden Park, Auckland, Saturday 25 August
Wallabies 23 v South Africa 18 at Suncorp Stadium, Brisbane, Saturday 8 September
Wallabies 19 v 23 Argentina at Cbus Super Stadium, Gold Coast, Saturday 15 September
South Africa v Wallabies at Nelson Mandela Bay Stadium, Port Elizabeth, Sunday 30 September
Argentina v Wallabies at Padre Ernesto Martearena Stadium, Salta, Sunday 7 October
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