The Dale Steyn-led South African pace attack bowled Australia out for 152 and then their batters chased it down with six wickets in hand to hand Australia a crushing defeat in what marked their beginning of a long home summer at Perth.
Australia have now lost 15 of their last 20 ODIs with three of them being no results, which is their worst ever run in the fifty overs format in recent memory.
Nathan Coulter-Nile (34) and Alex Carey (33) were the only ones to offer any resistance, with Andile Phehlukwayo the pick of the South African bowlers with 3 for 33 off six overs.
The Proteas opted for a four-pronged pace attack on a fast pitch and after winning the toss and choosing to bowl it quickly paid dividends with Australia soon in trouble.
Travis Head got a thick edge to Quinton de Kock off veteran quick Dale Steyn for just one and then D'Arcy Short, in the side for Shaun Marsh who needs minor surgery on an abscess, followed him back to the pavilion for a duck two balls later.
Again the dangerous Steyn did the damage, with Short driving a swinging ball into the hands of skipper Faf du Plessis who held a flying catch at second slip to leave Australia 4/2.
Captain Aaron Finch, who can be explosive when in full flight, totally misjudged the bounce from a Lungi Ngidi delivery and was out lbw soon after for five.
He mistakenly opted not to review with Australia floundering at 8-3 as replays revealed the ball would have gone over the stumps.
The first four of the innings didn't come until the 12th over when Chris Lynn drove a full-toss to the boundary but he couldn't build on the momentum, caught behind for 15 on review after the umpire initially gave him not out.
Another review saw a fuming Glenn Maxwell gone for 11 with Phehlukwayo just getting his fingers under the ball for a catch at mid-on.
Left-hander Carey, in the side as wicketkeeper after Tim Paine was dropped, kept the scoreboard slowly ticking over but he fell attempting to scoop an Imran Tahir ball over the head of de Kock.
Some late fireworks from Coulter-Nile, including a big six, took Australia past 150.
In reply, South African openers de Kock (44) and Hendricks (47) got off to a solid start putting 97 runs for the first wicket. The pitch also eased up considerably but the duo impressed with their back foot play to bury any hopes of an Australian comeback.
Australia did pick up a few quick wickets towards the end with all-rounder Marcus Stoinis returning with figures of 3 for 16 but that did not alter the inevitable.