Michael Hussey, named man of the series, played a vintage unbeaten knock of 45 from 64 to guide Australia past South Africa's target of 222 for 6 with 15 balls to spare. He brought up victory with an emphatic pull shot for six.
The predicted rain never eventuated and the Proteas apparent plan of preserving wickets backfired. Their 17 runs from the batting power play was a telling factor in their slow run rate of just 4.4 an over.
The Australians made life difficult for themselves in chasing, with poor shot selection resulting in the fall of regular wickets. But in the end they showed why they're the No.1 ranked team in one-day cricket, after victories in Centurion and now Durban outweighed their one off-night in Port Elizabeth in game two.
Returning from back spasms, Shane Watson justified Australia's eagerness to have him play, even with the two Test matches just around the corner. Watson was outstanding with the bat, posting 49 from 46 balls to get Australia off to the perfect start and earn him man of the match honours.
Another injury-hampered star also played part in a patient Australian chase. Shaun Marsh scored 30 in his return from a shoulder problem which kept him out of the opening two matches of the series.
That combined with a steady contributions by captain Clarke (26), and Brad Haddin (23) and the anchoring role from Hussey saw Australia to the finish line despite some nervous moments.
Proteas part-timer JP Duminy (2 for 29) took the important wickets of Clarke and Marsh, and when the West Australian fell the score was 156 for 5 in the 35th over, when another quick wicket would have given South Africa a big opportunity to steal the match back.
Australia's decision to go with a long specialist batting line up paid dividends on a slowing Kingsmead wicket, where they now hold a commanding 5-2 advantage over the home side. Earlier, Australia produced a mature bowling performance in the field.
Tasmanian spinner Xavier Doherty was the standout bowler for Australia, taking 2 for 34 from nine overs. Young quick Pat Cummins was destroyed in his opening spell, but showed excellent composure to fight back in his second effort to finish with 1 for 49.
South African captain Hashim Amla and Test skipper Graeme Smith (19) opened the batting with a 58-run partnership. Amla was in fine touch before being senselessly run out in the 26th over for 53.
Jacques Kallis made his second straight half century to become the fifth highest run scorer in the history of ODIs.
The star all-rounder combined with Amla for a second-wicket partnership of 59, but wasn't able to kick on to a big score either and was out for 54 when he skied Doherty to the boundary in the 34th over. Mitchell Johnson finished with 2 for 37.