Australian Marnus Labuschagne's first one-day international century proved to be in vain as South Africa breezed to a six-wicket victory in Potchefstroom on Saturday and a clean sweep of the three-match series.
After being sent into bat, Australia posted a below-par 254 for seven in their 50 overs, with South African-born Labuschagne hitting a run-a-ball 108 to bolster an otherwise mediocre effort from the visitors.
The home side always looked in control of their chase, JJ Smuts playing the anchor role with a career-best 84 and ably supported by other new faces Kyle Verreynne (50) and Heinrich Klaasen (68 not out) as they romped to victory with 27 balls remaining.
South Africa continued their recent dominance of Australia in this format having won 11 of their last 12 ODI meetings dating back to 2016.
"We have not been at our best, we have been good in patches and then let our foot off the gas," Australia captain Aaron Finch said at the post-match presentation.
"Credit to South Africa, they put us under pressure with bat and ball. We only took 12 wickets in the series, but all round we have not been at our best."
Australia struggled to get going in their innings, managing just 39 in the first 10 overs for the loss of David Warner (4) and were three down for the addition of another 16 runs as South Africa picked up the key wickets of Steve Smith (20) and Finch (22).
Finch was a debut wicket for South African seamer Daryn Dupavillon (1-21), who was in the team after the home side rested the spearhead of their attack, Lungi Ngidi.
Labuschagne set about rebuilding the innings, though, as he put on 81 for the fourth wicket with D'Arcy Short (36) and 53 for the fifth with Mitchell Marsh (32).
He reached his maiden ODI century off exactly 100 balls, much to his delight and that of a sizeable group of family and friends in the stands.
South Africa's chase came at a good rate, with Smuts's 84 coming off 98 balls, including 12 fours, before he fell with his hundred, and victory, in sight.
He added 96 with Verreynne for the third wicket, a partnership that laid the platform for a comfortable victory as man of the series Klaasen smashed the winning runs with a six to take his tally in the three matches to 242.
South Africa now embark on a three-game ODI tour of India starting on Thursday, while Australia return home to host New Zealand in a limited-overs tour beginning on Friday.