Chasing a target of 292 runs, Australia did not get off to a good start as Lungi Ngidi removed both the openers cheaply.
Ex-Proteas captain Faf du Plessis is being rested along with recent regular players in Rassie van der Dussen and Dwaine Pretorius.
In the match between Australia and RSA, Ngidi was called by the on-field official for over-stepping during the 16th over but replays showed his foot had landed behind the line.
Quinton de Kock was named man of the match after he slammed 70 off 47 balls to get the home team off to a blazing start.
But both players were constantly booed and jeered during last year's one-day World Cup and Ashes series in England, and they are expected to receive similar treatment in South Africa.
Australia finished the fourth day one wicket short of victory with South Africa on 293 for nine, needing 417 to win.