Australia were bowled out for 246 in their first innings, giving South Africa a lead of 177, which they stretched to 369 by the close of play, reaching 192 for four. Hashim Amla returned to form with a sparkling innings of 93 not out.
But South Africa will be without left-arm fast-medium bowler Wayne Parnell when they attempt to bowl out Australia a second time. Parnell, who on Friday, took two wickets with his first three deliveries of the match, pulled up with a groin injury after bowling three balls in his ninth over.
It left South Africa with three specialist bowlers after bringing in a batsman for an all-rounder after losing the first Test in Centurion by 281 runs.
Australia found themselves in unfamiliar territory in a dominant southern hemisphere summer, during which they have won six successive Tests, all by wide margins.
South Africa, though, looked more like the team that has surged to the top of the international Test rankings as they followed up a solid first innings with aggressive bowling to put Australia under pressure.
South Africa were on top from the fifth over of the day when Philander had top-scorer David Warner caught at slip for 70 runs.
Nightwatchman Nathan Lyon, after standing up to a bumper barrage from Morkel, chopped a ball from the tall fast bowler into his stumps in the next over.
Steve Smith and Brad Haddin both survived chances as they added 40 for the seventh wicket before Haddin was bowled by Dale Steyn.
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