South Africa had already clinched the five-match series with one encounter left to play in Cape Town on Wednesday.
Kyle Abbott took four wickets as Australia were bowled out for 167 in just 36.4 overs, leaving South Africa with a modest target to chase. They did so successfully, reaching 168 for the loss of four wickets in 35.3 overs.
In the three previous ODIs, South Africa’s batsmen dominated the inexperienced Australian attack but on Sunday it was their bowlers who took centre stage.
Abbott bowled both Aaron Finch and David Warner in his opening two overs and finished with 4-40 in his first game of the series.
Wrist spinner Tabraiz Shamsi, making his home debut, took 3-36 as six Australians were dismissed leg before wicket, equalling the record number of lbw dismissals in an ODI innings. Mitchell Marsh scored 50 before becoming the sixth wicket to fall while wicket keeper Matthew Wade’s contribution of 52 helped add 46 runs for Australia's ninth wicket. In reply, South Africa were two wickets down for 29 runs before Du Plessis and JP Duminy steadied the ship and set them on course for a potential clean-sweep of the series.
Du Plessis was patient, although he should have been out on 17 when Adam Zampa spilled a simple catch. Rilee Rossouw finished 33 not out, thrashing the winning runs through the covers.
(Reporting by Mark Gleeson; Editing by Toby Davis)
