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The pair came together at 55-3 in the 16th over with Miller swatting 139 for his fifth limited-overs century and du Plessis smashing 125 — his 10th one-day ton.
Mitchell Starc, with 2-57, was the best of the Australian bowlers who were ruthlessly taken apart in the later overs.
The series is all square with the Proteas winning the opening game by six wickets and Australia snapping their seven-game losing streak to clinch the second by seven runs.
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Both sides opted for unchanged line-ups and, after winning the toss and putting the visitors into bat, Australia got a dream start with Quinton de Kock out in the third over.
Mitchell Starc did the damage, bowling a perfect line and length, with de Kock getting a tickle on the ball and wicketkeeper Alex Carey taking the catch.
Reeza Hendricks was dropped by Travis Head on eight, but was gone five balls later when Marcus Stoinis was brought into the attack and Carey took another good catch.
Aiden Markram smashed three sixes, including one huge blow off Marcus Stoinis that went out of the ground and down the street, with a new ball needed, on his way to 32.
But as he looked set for a big score, he tried to flick a Starc delivery down the leg side and Carey grabbed his third catch of the game to leave South Africa struggling.
Then hard-hitting Miller joined skipper du Plessis and the scoreboard began racing along.
Du Plessis was dropped on 29 and Miller escaped an lbw dismissal on 41 that was overturned on review.
They made the most of their second lives and began swinging their bats as du Plessis reached his century in 105 balls with 11 fours and one six before falling to Stoinis going for another big hit at the death.
Miller made the landmark in 95 balls, including eight fours and two sixes, and was finally caught at deep midwicket off Josh Hazlewood in the last over.