Marco Jansen claimed a sensational five-wicket haul as South Africa skittled Australia for 99 to enforce the follow-on, but Travis Head led a spirited fightback on day four in Gqeberha.
Australia declared at 314/6 after a rapid cameo from Pat Cummins, setting South Africa a daunting 421-run target on Day 4 of the first Test in Durban before Josh Hazlewood struck early blows.
South Africa's seam attack left Australia reeling at 124/6 before an unbeaten stand between Matt Renshaw and Pat Cummins guided the visitors to 187/6 ahead of an early stumps due to bad light in Durban.
Australia sealed a 45-run DLS victory against South Africa in the rain-affected third ODI at Potchefstroom, concluding the series with an encouraging performance praised by captain Mitchell Marsh.