Australia, who will clinch the five-game series if they win in Melbourne, made four changes to the team that beat the Proteas by 73 runs in Canberra on Wednesday.
Spinning all-rounder Glenn Maxwell, all-rounder James Faulkner and pacemen Pat Cummins and Nathan Coulter-Nile came into the Australian side.
The Proteas also made four changes in a bid to keep the series alive for Sunday’s final match in Sydney.
The South Africans have brought in Ryan McLaren, Robin Peterson, Wayne Parnell and Kyle Abbott.
Australia have never beaten South Africa in six ODIs at Melbourne Cricket Ground.
Australia – George Bailey (capt), David Warner, Aaron Finch, Shane Watson, Steve Smith, Glenn Maxwell, Matthew Wade, James Faulkner, Pat Cummins, Nathan Coulter-Nile, Mitchell Starc.
South Africa – AB de Villiers (capt), Quinton de Kock, Hashim Amla, Faf du Plessis, David Miller, Farhaan Behardien, Ryan McLaren, Robin Peterson, Wayne Parnell, Dale Steyn, Kyle Abbott.