Aiden Markram and David Miller hit half-centuries as the Proteas posted 315-9 in the series-deciding fifth ODI at the Wanderers on Sunday.
There was redemption for Australia leg-spinner Adam Zampa, who bounced back from conceding a world record-equalling 113 runs in the fourth match in Centurion on Friday when he bowled Heinrich Klaasen for six.
Klaasen slammed 174 off 83 balls in Centurion and was particularly harsh on Zampa but on Sunday he was beaten by a quicker ball from Zampa which deceived the batsman.
Zampa took two more wickets in the 48th over to finish with 3-71.
Australia captain Mitchell Marsh sent the Proteas in for the third match in a row despite his team having lost the previous two – but his reading of conditions proved correct as his pace bowlers extracted movement from the pitch for most of the innings.
Markram (93) and Miller (63) put on 109 for the fifth wicket and lower order batsmen Marco Jansen and Andile Phehlukwayo took the total past 300 with some big hitting towards the end.
Jansen hit three sixes in scoring 47 off 29 balls and Phehlukwayo cleared the boundary four times in his unbeaten 39 off 19 deliveries.
© Agence France-Presse