Australia bowled out South Africa for 256 to win the fifth and final one-day international by 47 runs at the Wanderers on Friday.
The visitors, trailing 3-1 in the series, piled up 303 for seven earlier in the day after being put in to bat.
South Africa made a good start to their reply when opener Herschelle Gibbs followed his century in the fourth match in Port Elizabeth with a knock of 82.
He and Jacques Kallis (64) added 104 for the second wicket in 124 balls but there were few other innings of note as the home side were bowled out in 45.5 overs.
Off-spinner Nathan Hauritz trapped Gibbs leg before and Kallis was caught behind off Nathan Bracken.
AB de Villiers scored 38 but South Africa collapsed from 213 for four to 238 for nine.
The leaping Ben Laughlin took an outstanding catch on the deep mid-wicket boundary to remove Albie Morkel for five off Hauritz's bowling.
Fiery paceman Mitchell Johnson again led the way for Australia with three for 58.
Earlier, Australia openers Michael Clarke and Brad Haddin put on 127 in 115 balls after South Africa had won the toss.
Medium-pacer Albie Morkel ended the stand when Haddin (62) sliced a lofted drive to cover where JP Duminy took a good, running catch.
Duminy again showed his speed across the field three overs later when he caught Clarke (66) off Roelof Van der Merwe.
Mike Hussey (49 not out), Callum Ferguson (41) and captain Ricky Ponting (40) then chipped in as Australia went past the 300 mark.
Duminy was the most effective South African bowler with three for 48 while fellow spinner Van der Merwe took two for 44.