South Africa managed just 96 in reply to Australia's total of 193-5 as the tourists dominated the series decider in Cape Town.
Keshav Maharaj is back in the ODI fold for South Africa, but Faf du Plessis will sit out again against Australia.
Jhye Richardson will remain in South Africa after Australia announced their squad for a series against New Zealand from March 13-20.
South Africa levelled the Twenty20 series against Australia at 1-1 thanks to some excellent bowling in the closing overs.
South Africa were skittled for 89 by Australia at the Wanderers, as leg-spinner Ashton Agar took five wickets including a hat-trick.
Ashton Agar claimed career-best Twenty20 international figures, including a hat-trick, as Australia won handsomely in Johannesburg.
David Warner was embroiled in controversy in Australia's last tour of South Africa, but he is not expecting tensions to boil over this time.
Steve Smith says he has been given a warm welcome in South Africa, but is expecting hostility when he faces the Proteas.
Jordan Petaia, who saw his 2019 season blighted by a foot injury, has suffered another setback that will end his Super Rugby season.
South Africa must cope without injured opener Temba Bavuma for the first Twenty20 clash of their three-match series against Australia.