Australia fought back and South Africa suffered an injury blow on the third day of the fourth Test at the Wanderers Stadium on Sunday.
Australia reached 201 for seven at lunch after adding 91 runs to their precarious overnight position of 110 for six. They were 287 runs behind South Africa's first innings total.
South African fast bowler Morne Morkel, playing in his final Test, had to leave the field with a side strain as Australian captain Tim Paine (47 not out) and Pat Cummins (50) built a defiant 99-run partnership.
A message from the South African dressing room said Morkel had suffered a similar injury to that which kept him out of action for two months earlier in the season, although he was receiving treatment and it was hoped he would be able to take the field later in the match.
Morkel's injury, which reduced South Africa to three front-line bowlers, and Australia's fightback virtually eliminated any chance of South Africa enforcing a follow-on and trying to claim an early, series-clinching win. South Africa lead the series 2-1.
Paine, who took over the captaincy after skipper Steve Smith and deputy David Warner were sent home for ball tampering in the third test, was batting with a hairline fracture of his right thumb, sustained while keeping wicket on Saturday.
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He and Cummins defied the South African bowlers until shortly before lunch when Cummins missed a sweep and was leg before wicket to left-arm spinner Keshav Maharaj.
Cummins made a career-best 50 off 92 balls with six fours and a six.