On a chaotic morning when Steve Smith ruled himself out with a neck injury, Australian captain Pat Cummins sent the Proteas in on a straw-coloured pitch under largely blue skies.
Australia's start then became their worst after electing to bowl first in a game in 56 years, with Aiden Markram (78) and Marques Ackerman (95) putting on 158 for the first wicket.
But Nathan Lyon changed the innings' momentum, having a charging Ackerman stumped then bowling Temba Bavuma for a duck as the Proteas lost 4-58.
The wickets came with the spinner recalled to the team in place of Scott Boland, who was again Australia's unlucky man after his five-wicket haul last week.
Mitchell Starc also took a diving catch at backward-square-leg to have Markram's wicket on Tuesday, when he skied Josh Hazlewood high into the Cape Town air trying to pull.
And Cooper Connolly got Matthew Breetzke lbw for two, when Australia reviewed a shout that showed it hit pad before bat with the ball on track to take middle stump.
The fightback may relieve some of the initial blowback around the toss call, which was questionable from the moment Markram pulled Cummins' fifth ball for six.
At that point, the Test was only 6.5 overs old.
Ackerman hit another one over long-off from Lyon shortly after he was brought on in the 11th over, before taking Cummins over fine leg for the morning's third six.
In all the Proteas hit 23 boundaries in the first session alone. Australia's morning was summed up when Markram hit Starc straight to cover on 39, only to see Travis Head put down the simplest of catches.
Starc's reaction, as he put his collar between his teeth, said it all.
Ackerman raised his half-century off 62 balls, before also hitting Starc for four straight boundaries through mid-wicket and gully before lunch.
But when Lyon smartly darted a ball out wide with Ackerman keen to charge him after lunch, the left-hander fell and the tourists saw an opening.
Australia's position could have been even better, had Marnus Labuschagne got a hand to a David Bedingham chance on 16 off Hazlewood. The Proteas No.3 has since reached 41no.
Australia's return to Cape Town for a Test for the first time since the 2018 ball-tampering scandal had earlier began in dramatic fashion, with Smith's neck the point of focus.
The 37-year-old arrived before the rest of the team and was spotted appearing frustrated in the nets, before making the call that he was not right to play.
That prompted Cummins to say at the toss that Australia "had to look elsewhere", with Josh Inglis called in for his first Test since last summer.
Boland, Nic Maddinson and Beau Webster were dropped following last week's thrashing in Gqeberha, with Lyon, Connolly and the fit-again Cameron Green all coming in.
The four changes are the most Australia has made mid-series since the ball-tampering scandal.
South Africa can take top spot in the ICC rankings from Australia with victory at Newlands.
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