Alex Carey grabs maiden test century to put Australia firmly in charge against South Africa
The Proteas were 15 for one, still needing 371 runs to make Australia bat again, when play was stopped seven overs after tea at the Melbourne Cricket Ground and later abandoned.
With Carey scoring 111 and all-rounder Cameron Green contributing an unbeaten 51 with a broken finger, the hosts piled on the runs before declaring at 575 for eight under gathering clouds.
South Africa captain Dean Elgar was then caught behind for a duck off the bowling of home skipper Pat Cummins, continuing a dismal series for the seasoned opener.
Opener Sarel Erwee was seven not out and number three Theunis de Bruyn was on six, the latter having been dropped by David Warner in the slips off Cummins.
With drizzle falling and the ball skidding on a damp pitch, Erwee and De Bruyn headed off gratefully when play was halted.
But Australia will be confident of taking the remaining wickets and avoid batting again.
They skittled the tourists for 189 in the first innings and less in the first test win in Brisbane.
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Following Warner's double-century on day two and Green's five-wicket haul on day one, Cummins's team dominated for a third successive day, with South Australian Carey leading from the front.
He had good support from Green, who bravely soaked up 177 balls despite nursing a broken finger that saw him retire on day two.
The pair built a 117-run partnership as South Africa's bowlers failed to build on a positive start after taking four wickets in the morning.
"It was nice to be able to consolidate on our start from yesterday," said Carey, who was on nine when Australia resumed in the morning at 386 for three.
"To see (Green) put on a brave face, bat beautifully ... it allowed us to put on a really good partnership."
Carey pulled Marco Jansen for three to bring up his century but was later caught and bowled by the all-rounder after sending a top-edge high above the pitch.
It could have been a better day for South Africa had their bowlers kept up the pressure after grabbing four early wickets.
Anrich Nortje struck twice in two balls, bowling Travis Head for 51 and then Warner on the next delivery with a sizzling yorker after the veteran opener resumed on 200, having retired hurt with cramp on day two.
Cummins survived the hat-trick ball but was caught behind for four off the bowling of paceman Kagiso Rabada.
South Africa had taken three wickets for five runs, leaving Australia 400 for six, but the rally stalled as plucky tail-ender Nathan Lyon (25) combined with Carey in a quickfire 40-run partnership.
Though Green batted superbly with his injury, the big all-rounder will not bowl for the rest of the test and has been ruled out for the third and final match in Sydney.
Fast bowler Mitchell Starc was also nursing a sore finger on his bowling hand but showed ample pace and swing in his few overs before the rain.
Carey was confident Australia had enough in their attack to take care of business in Melbourne.
"The way that (Starc) is bowling, I don't have too many concerns for this match," he said.
"Pencil Gaz (Lyon) in for a heap of overs .... I feel like we've got enough bowling."