The Proteas were fired by a devastating early spell of fast bowling from Dale Steyn.
Openers Graeme Smith and Alviro Petersen extended the lead with 24 runs without loss before the tea break to put the tourists on the front foot in their bid to win the series and retain their number one test ranking.
Steyn (4-40) was ably supported by fellow quicks Vernon Philander (2-55) and Morne Morkel (1-19) in knocking over the top order in bright Perth sunshine before spinner Robbie Peterson mopped up the tail with 3-44.
Only wicketkeeper Matthew Wade, who scored a bright 68, and debutant pace bowler John Hastings, the last Australian out for 32, offered any real resistance to the South African bowling attack.
Australia had resumed at 33-2 chasing South Africa's first innings tally of 225 in front of a big WACA crowd hoping to see Ricky Ponting score a century in his penultimate test innings.
They did not have to wait long to give the former Australia captain a standing ovation but it was Steyn who was stealing the limelight.
The world's top ranked bowler had failed to fire in the previous two drawn tests of the series but he hit his straps in the first 40 minutes with three wickets at the cost of just four runs.
The first ball of the 29-year-old's first over dispatched opener David Warner caught behind for 13 after a lengthy delay for a fruitless TV appeal, while his fourth sent nightwatchman Nathan Lyon back to the pavilion for seven.
Ponting, meanwhile, had got off the mark with a single through the offside but had added just three more runs when he was trapped lbw by Philander.
The 37-year-old's appeal to the TV umpire had less merit than Warner's but was just as fruitless.
With their free-scoring captain Michael Clarke at the crease, Australia's hopes of a first innings lead were still alive but Steyn soon all but squashed them with his best ball of the series
A fullish effort delivered at full pace that moved away at the last moment, the delivery induced Clarke into an edge that AB de Villiers collected behind the stumps.
Almost certain runout
Wade, playing with the philosophy that the best form of defence is attack, set about steadying the ship in bullish fashion.
Building a partnership of 55 with Mike Hussey, the wicketkeeper brought up his second test half century from 51 balls by launching his third six over the deep midwicket boundary.
Hussey, who scored centuries in the previous two tests of the series, departed soon afterwards, caught in the slips off Morne Morkel having eked out 12 runs in 68 minutes to leave the hosts on 100 for seven.
Hastings survived an almost certain runout when he was on four soon after lunch when Dean Elgar missed with his attempt to hit the stumps with the batsman stranded.
Peterson, recalled for his first test in four years, then got some revenge for the two sixes Wade had hit off him when the Australian missed attempting a slog and was clean bowl.
Mitchell Johnson, who has a test century and six 50s to his name, then belied his reputation as a strong tailender with an impatient swipe at a Peterson delivery and went for seven in similar fashion.
Hastings survived another two overs before his slog off Peterson was gathered in brilliant style by Alviro Petersen, who flicked the ball into the air as he fell over the boundary rope and returned to the field to take the catch. – Reuters