Ed Cowan's maiden international century and an unbeaten double ton from captain Michael Clarke ensured that any hopes South Africa had of forcing a result in the first Test were all but wiped out at the Gabba after the hosts finished day four on 487 for four.
Chasing the Proteas' first innings effort of 450, Cowan hit 136 in a partnership of 259 with his skipper, before finally suffering an unfortunate run out to be the only the wicket of the day in Brisbane.
Clarke, who plundered 150 against the same opposition in Cape Town last year, finished the day on 218 with Michael Hussey (86no) picking up where Cowan left off to give the home side a lead of 37 runs.
In two and a half hours of cricket before lunch Australia scored 103 runs with barely a scare and such was the unthreatening nature of the South Africa attack that Graeme Smith, who is without a frontline spinner in this game, chose to bowl himself.
By lunch, the partnership, which began with Australia in real danger on 40 for three, had reached 174.
Cowan pulled Vernon Philander for four in the second over after the resumption and that briefly seemed to free both batsmen, Clarke taking three fours off the next Morne Morkel over to move into the 90s.
Clarke took a single to bring up the 200 stand, then crept towards 100 before finally reaching the milestone in similar fashion.
A mix-up between Dale Steyn and Jacques Rudolph in the deep saw Cowan dropped on 123, but Steyn made up for his part in the error when he got a finger to the ball to run the same batsman out backing up just before tea.
After tea Clarke got an inside edge through to wicketkeeper AB de Villiers from a Morkel no-ball.
Clarke reached his third double century of 2012 with an immaculately timed on drive boundary off Steyn.