The Australians reached lunch at 43 for six after being sent in to bat on a juicy strip with skipper Steve Smith fighting a lone hand on 20 and Test newcomer Joe Mennie on 10.
Australia just managed to scrape past their lowest-ever first innings total of 42 in a home Test made against England in 1888.
Vernon Philander was South Africa's destroyer with the figures of three for three before he was forced from the field with a shoulder injury after a mid-pitch collision with Smith while making a leg before wicket appeal.
It was an irresponsible shot from the Australian vice-captain and things only got worse in Kyle Abbott's following over when recalled Joe Burns was trapped leg before wicket.
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The home side had lost both openers for just two runs as Usman Khawaja and skipper Steve Smith came together on a perilous pitch.
Khawaja lasted until the ninth over until he edged Philander to Hashim Amla at slip for four and Adam Voges was out next ball, caught behind by de Kock, with Callum Ferguson facing a hat-trick ball in his first Test at eight for four.
Philander was forced to leave the field for shoulder treatment but in the next over Ferguson was brilliantly run out for three by a direct throw by fielding substitute Dane Vilas while going for a second run.
Wicketkeeper Peter Nevill was the sixth wicket to fall after a DRS review of a lbw appeal off Kagiso Rabada with nothing going Australia's way.
The Australians are looking to fight back from a comprehensive 177-run loss to the Proteas in the series opener in Perth with the team coming under heavy criticism over their capitulation.
The South Africans earlier named Kyle Abbott in their only change in the absence of injured strike bowler Dale Steyn.
Australia dropped all-rounder Mitchell Marsh and gave Test debuts to batsman Ferguson at No.6 and paceman Mennie, while Burns replaced injured opener Shaun Marsh.
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