The hosts wrapped up a 4-1 series triumph despite a late wobble in Sydney, eventually reaching the revised target of 275 with five balls to spare after rain reduced Australia's innings to 48 overs.
James Faulkner found the boundary for the winning runs under considerable pressure after a flurry of wickets from a resilient South Africa - who scored 280-6 - in the closing overs.
The result ensures Australia will enter 2015 - an ODI World Cup year - as the top nation in the 50-over format of the game.
However, it could have been a very different story after Robin Peterson (4-32) produced a destructive spell of bowling as Australia lost four wickets for the addition of just three runs between the 41st and 46th overs.
Just as the contest looked to be turning in the tourists' favour, though, a no ball from Kyle Abbott (1-59) in the penultimate over eased the pressure on the struggling home side, who survived the scare to see the job through.
Needing four off the final over, Faulkner took the shortcut to victory and played a well-timed sweep to the ropes to spark celebrations from the majority of the SCG crowd.
South Africa had built a defendable total on the solid foundations of Quinton de Kock's 107, ably assisted by Rilee Rossouw's steady 51.
Farhaan Behardien put on an eye-catching 63 lower down the order, consisting of seven fours and two sixes, but the assiduous efforts of Pat Cummins (3-54) with the ball kept the visitors in check.
Australia mounted a response fitting for a side with designs on reclaiming the summit of the ODI rankings, David Warner (21) and Aaron Finch (76) scoring quickly to provide a promising platform for success.
Following Warner's dismissal to Wayne Parnell (1-54), the rain interrupted their progress before a decision was taken to reduce the reply to 48 overs.
Finch subsequently put on a 100-run partnership with Shane Watson (82) before falling to the excellent Peterson.
Steven Smith (67) was the only other Australian to make a double-figure contribution, with the rest of the batting line-up almost contriving to snatch defeat from the jaws of victory.
It was Smith's departure, when Australia needed only 11 runs with four wickets and 25 balls remaining, that prompted the late panic.
George Bailey added only four runs, Matthew Wade just three, and Cummins was out for a second-ball duck as Peterson looked to steal the headlines.
But when Abbott overstepped his mark, the momentum was halted in an instant and it fell to Faulkner to finish the job in style.