Australia put South Africa on back foot
The overhauled Australian pace bowling unit had reduced the tourists to 6-75 with five quick wickets around the lunch break but du Plessis once again proved unmovable until he ran out of tailend partners when unbeaten on 78.
Dale Steyn gave the tourists a quick boost in the late afternoon light when he had opener Ed Cowan caught for a golden duck with his third ball before Vernon Philander removed Shane Watson lbw for 10 after an appeal to the TV umpire.
Opener David Warner, who was unbeaten on 12, and nightwatchman Nathan Lyon, who had made seven, will resume on day two of a Test which will decide which of the countries will be number one in the Test rankings.
Australia's selectors had earlier been vindicated in their decision to rest Ben Hilfenhaus and Peter Siddle after the pacemen had run themselves into the ground in Adelaide in the wake of a series-ending injury to James Pattinson.
Recalled seamers Mitchell Starc, Mitchell Johnson and debutant John Hastings all got among the wickets to leave South Africa perhaps ruing the decision to bat first on a bouncy WACA track.
All-rounder Watson, who missed the two drawn Tests in Brisbane and Adelaide with a calf injury, made the first breakthrough with 38 runs on the board when he had Graeme Smith caught in the slips by Michael Clarke for 16.
The South Africans were looking like they might just survive until lunch, albeit with a modest total, before the intervention of left-arm quick Starc.
Two full, late-swinging deliveries in six balls fooled first opener Alviro Petersen (30) and then all-rounder Jacques Kallis (2) and ripped through the gate to make a mess of the stumps.
There was to be no respite after lunch and Hashim Amla had already been dropped by Cowan when he was run out by Warner's direct hit without adding to his tally of 11.
Cowan's spill deprived Hastings of his first Test wicket but the bowler did not have to wait long to claim it as he found some late movement to have AB de Villiers caught in the slips for four.
South Africa were now well and truly on the rack and it got worse when Johnson finally got some reward for some fine swing bowling with the first of his two wickets.
The sometimes erratic 2009 ICC World Player of Year has struggled with form and fitness in the year since his last Test but he proved once again he is a fearsome prospect at the WACA.
Dean Elgar's first Test innings lasted just 18 minutes and 12 balls before he caught a top edge with an attempted pull and Matthew Wade took the catch behind the stumps to hand the debutant a duck.
India collapsed from a similar position here last year and Warner had scored a 69-ball century by the end of the first day's play with Australia winning inside three days.
South Africa are made of sterner stuff, however, and du Plessis anchored a stand of 57 with Robin Peterson, 64 with Vernon Philander and 19 with Morne Morkel to triple his country's tally for the last four wickets.
Coming after the 78 and unbeaten 110 he scored to save a draw on his Test debut in Adelaide, the 28-year-old now boasts a Test batting average of 266. Lyon broke up all three of du Plessis's big partnerships to finish with figures of 3-41, ending South Africa's innings when he had Morkel caught by Hastings.
Lyon faced the South Africans again with bat in hand sooner than he would have liked to protect the wicket of Ricky Ponting, who is playing his 168th and final Test in Perth.
SOUTH AFRICA (I Innings):
Smith c Clarke b Watson 16
Petersen b Starc 30
Amla (run out) 11
Kallis b Starc 2
De Villers c Clarke b Hastings 4
Elgar c Wade b Johnson 0
Du Plessis (not out) 78
Peterson c Wade b Lyon 31
Philander c Hussey b Lyon 30
Steyn b Johnson 2
Morkel c Hastings b Lyon 17
Extras (LB-2, W-2) 4
Total (all out, 74 overs) 225
Fall of wickets: 1-38, 2-61, 3-63, 4-67, 5-67, 6-75, 7-132, 8-196, 9-206.
Bowling: Starc 16-3-55-2, Hastings 20-2-51-1, Watson 9-2-22-1, Johnson 17-3-54-2, Lyon 12-1-41-3.
AUSTRALIA (I Innings):
Warner (batting) 12
Cowan c Kallis b Steyn ....0
Watson lbw Philander 10
Lyon (batting) 7
Extras (LB-4) 4
Total (for 2 wkts, 11 overs) 33
Fall of wickets: 1-3, 2-18.
Bowling: Steyn 6-2-21-1, Vernon Philander 4-0-8-1, Morne Morkel 1-1-0-0.