Proteas captain Temba Bavuma struck his fifth Test century, and the best of his career, as the hosts dominated Australia on the third day of the second Test at St George's Park in Gqeberha.
South Africa suffered two wickets after lunch to end day one on 20/2 after only 12.2 overs in a rain affected second Test at St. George's Park on Sunday.
Australia allrounder Cameron Green is unlikely to be risked for the second Test against the Proteas, that starts in Gqeberha on Sunday, as he recovers from an abdominal strain.
Aiden Markram battled for almost six hours at the crease but a career-best bowling effort from Josh Hazlewood saw Australia complete a 214-run win against the Proteas in the first Test in Durban.
The Proteas will face a battle on the final day to save the opening Test against Australia in Durban, going to stumps on 102-4 after being set a target of 421.
Australia have earned a 139-run lead over South Africa after bowling out the lacklustre hosts for 284 runs in their first innings at Kingsmead Stadium on Sunday.