Paarl: Heinrich Klaasen's first one-day international century successfully set up South Africa for a 74-run win as Australia were bowled out for 217 while chasing 292 in the series-opener on Saturday.
Klaasen, often on the fringes of South Africa's limited-overs teams, made 123 not out from 114 balls as the home team posted 291-7 in Paarl.
Klaasen had only one previous half century in ODI cricket and was playing his first one-dayer in more than a year.
South Africa were 48-3 in the 10th over, having lost Janneman Malan first ball of the game on his debut, lbw to Mitchell Starc.
Klaasen set about rescuing the innings with his seven fours and three sixes.
David Miller supported with a 70-ball 64. Kyle Verreynne also helped with 48 on his ODI debut.
Australia threatened with an 84-run stand for the third wicket between Steve Smith (76) and Marnus Labuschagne, who made 41 against his country of birth.
Labuschagne's first game against South Africa, the country he left at the age of 10 when his family emigrated to Australia, ended when he was caught trying to hit spinner Keshav Maharaj down the ground.
The turning point came when Smith was out lbw to fast bowler Anrich Nortje to leave Australia 174-5.
It started a collapse, where the Australians lost their last six wickets for 43 runs to be bowled out in 45.1 overs.
Lungi Ngidi took 3-30 for South Africa and Nortje 2-39. Nortje ended it by knocking back Josh Hazlewood's off stump to put the Proteas ahead in the three-match series.