A century from Duminy and a record-breaking ninth-wicket partnership saw SA gain the upper hand over Australia.
The scorecard from the MCG
Duminy made a superb 166 while Dale Steyn, who was handed three reprieves, made a career-best 76 as South Africa were eventually bowled out for 459 in their first innings - a total which seemed fanciful at the start of the day.
Thankfully for the home side Matthew Hayden, potentially fighting for his career, and Simon Katich survived a testing two-over spell prior to stumps to leave Australia four without loss and trailing by 61 runs.
Clarke in dark over Ponting tactics
It took Australia, without paceman Brett Lee all day due to a foot injury, until 20 minutes before the close to claim the last of the four wickets they needed to end South Africa's innings.
Uncharacteristically poor fielding
The Proteas, who resumed on 198 for seven, are now dreaming of a stunning victory just 24 hours after staring at a heavy defeat.
And they have Duminy, playing in only his second Test, Steyn - whose previous Test best was 33 - and some uncharacteristically poor fielding from the Australians to thank for the stunning turnaround.
Duminy had shared a stand of 43 with Morne Morkel late on day two and added 67 with Paul Harris before uniting with Steyn.
Numbers from the MCG!
The pair's epic 180-run stand was the highest ninth-wicket partnership in Tests between the two countries and the third-highest overall - only 15 short of the previous record set by Mark Boucher and Pat Symcox in 1998.
Duminy, who last week kept the Australians at bay with a nerveless half-century on his debut as South Africa completed an exhilarating run chase to win the first Test in Perth, was again a thorn in the side of Ricky Ponting's men.
Batting with the maturity of a veteran Duminy - the last man out - served notice as a future Test star with an innings of pure class.
Harris was the first to prosper
The 24-year-old momentarily lost his rhythm after lunch when, with Steyn dominating the strike, Nathan Hauritz kept him tied down but he emerged through that tricky period and upon reaching the 90s, was gifted a five from four overthrows by the tiring Australian fielders.
He then recorded his century with a glorious cut shot and after rubbing salt into the wounds by edging Mitchell Johnson for consecutive boundaries, posted his 150 with an exquisite on-drive that found the rope.
Despite batting with the tail, Duminy's faith in his partners did not waver until he was joined by last man Makhaya Ntini and they more than repaid his confidence.
Harris was the first to prosper, hitting a brisk 39 before the part-time medium pace of Michael Hussey brought about his downfall as he was caught in the deep by Johnson.
That wicket fell at 11.12am and it was not until 4.20pm - when number 10 Steyn was eventually dismissed - that the Australians would again celebrate.
Steyn was spared on 32 by Ponting, who put down a relatively simple chance at second slip from the bowling of Johnson, and a run later by Hussey, who failed to even lay a finger on a high ball after losing it in the sun.
Hauritz, the victim of the second chance, then had nobody to blame but himself when he failed to complete a return catch from Steyn on 57.
Three minutes shy of four hours at the crease, Steyn eventually lost concentration and his wicket when he was bowled by Peter Siddle, the pick of Australia's bowlers with figures of four for 81.
Duminy eventually fell to a tired shot when he was caught by Siddle square of the wicket off Hauritz but not before adding another 28 with Ntini.
