After winning the toss and electing to bat, the Proteas were bundled out for 225 despite more heroics from Adelaide Test hero Faf du Plessis in a match that will decide the top-ranked nation in Test cricket.
However, the Proteas quickly struck back with a vengeance, claiming two Australian wickets in the hour before stumps.
Opener Ed Cowan was caught in slips by Jacques Kallis off pace spearhead Dale Steyn for a first-ball duck, before Shane Watson (10) was given out lbw to Vernon Philander on a decision review, after umpire Asad Rauf had turned down the initial appeal.
At the close, the home team were 33 for two, with David Warner on 12 and night watchman Nathan Lyon surviving a torrid examination from Steyn in the final over of the day to be seven not out.
While the South Africans were chasing a score of 300, recalled spinner Robin Peterson, who made 31 with the bat to be the second-highest scorer behind du Plessis' unbeaten 78, said the two late wickets had renewed the team's spirits.
"We have to make it (225) a good score," he said.
"But after being 6-75, we are pretty happy getting with scoring 225, and especially getting two wickets late in the evening.
"It made 225 look like a decent score, especially if we can get one or two wickets tomorrow morning."
Batting at number seven, second Test hero du Plessis again played a lone hand in the South African first innings and teamed with the tail to add vital late runs after the Proteas had slumped to 75 for six when they lost five wickets for 14 runs either side of lunch.
Debutant Australian paceman John Hastings conceded the home side had let the visitors off the hook and said the first hour of Saturday's second day would be crucial to the outcome of the match.
"We let it slip a little bit, but 225 is still a pretty good effort to bowl them out," he said.
"The wicket will get better and if we can bat well for an hour in the morning, I think it will flatten out nicely."
Australia were forced to completely revamp their fast bowling line-up for the match, with their three pacemen from the drawn Adelaide Test -- Peter Siddle, Ben Hilfenhaus and James Pattinson -- all ruled out.
Left-armer Mitchell Johnson was recalled for his first Test in 12 months, Mitchell Starc was promoted after being 12th man for the first two matches in the series, and Hastings was handed his Test debut.
All were in the wickets as they decimated the South African top order.
It was the returning Watson (1-22) who claimed the initial breakthrough, having Graeme Smith caught at first slip by rival skipper Michael Clarke for 16.
Watson made a welcome return from a calf problem, having missed Australia's last eight home Tests with various injuries, by finding a thick outside edge from Smith to remove the Proteas skipper.
Just before lunch, Starc (2-55) struck two telling blows.
Starc removed opener Alviro Petersen (30) when he bowled the right-hander with a full delivery and then found a way through the defence of Kallis (2), who overcame a hamstring injury to take his place in the match, with a similar ball.
Already struggling at 63 for three at lunch, the Proteas crumbled after the resumption, with Hashim Amla (11), AB de Villiers (4) and debutant Dean Elgar (0) all falling in quick succession.
Amla was run out by a brilliant direct hit from David Warner in the covers, de Villiers became Hastings' first Test scalp when caught at first slip by Clarke and Elgar gave Johnson (2-54) a well-deserved first wicket when he was caught behind.
Peterson and Philander (30) offered support to du Plessis, while Lyon picked up late wickets with his off-spin to claim 3-41.