Du Plessis made a cautious start, but found his feet quickly enough to reach his 50 off just 33 balls, and then went into overdrive in the last few overs to end up on 79 off 41 deliveries (5x4, 5x6) to give the South Africans the impetus they needed at the finish.
He was assisted by David Miller, who smashed 33 off 18 balls (2x4, 2x6) to resurrect the Proteas innings somewhat after they got into a tangle in the middle overs after Australian captain Steve Smith won the toss and chose to bowl first.
AB de Villiers once again missed out after hitting a four and six, getting an inside edge to a John Hastings ball that ricocheted on to his stumps to dismiss South Africa’s most destructive batsman for just 13.
But Quinton de Kock picked up the pace to allow Du Plessis to play himself in as the left-hander hit three consecutive boundaries off Josh Hazlewood to take the Proteas to 62/1 off their six powerplay overs.
The SA wicket-keeper did the same to Glenn Maxwell, but then he missed a slowish full toss from the skilful James Faulkner to be bowled off his pad for 44 off 28 balls (8x4, 1x6).
JP Duminy (14) walked to the wicket under some pressure to get a decent score after a lean run, and he played two glorious shots for a four and six, but the very next ball he tried to pull Mitchell Marsh over midwicket again and held out to Smith.
Miller came in and continued where he left off with a match-winning innings in Durban on Friday as he thrashed left-arm spinner Ashton Agar all over the park, but went for one too many and drilled Agar straight to Maxwell at long-off for 33.
The Proteas brainstrust probably made the wrong call to send in Farhaan Behardien at that point with five overs left, as he is more of an accumulator than a big-hitter. And so it proved as after both and Du Plessis just knocked the ball around for singles, Behardien hit a Faulkner full toss to Agar at midwicket to be out for three.
Chris Morris came in ahead of David Wiese with the hope of repeating his boundary exploits with the bat, but instead it was Du Plessis who took charge, hitting Hastings for two fours and two sixes in the last over before being caught by Maxwell for 79.
But after Morris went for three, Wiese hit the last ball for six to take the Proteas beyond the 200 mark.
Australia, though, have a strong batting line-up and will fancy their chances on a good Wanderers pitch and quick outfield.
Teams For Wanderers
South Africa: Quinton de Kock (wk), AB de Villiers, Faf du Plessis (captain), JP Duminy, Farhaan Behardien, David Miller, David Wiese, Chris Morris, Kagiso Rabada, Dale Steyn, Imran Tahir.
Australia: Aaron Finch, Shane Watson, Steve Smith (captain), David Warner, Glenn Maxwell, Mitchell Marsh, James Faulkner, Ashton Agar, Peter Nevill (wk), John Hastings, Josh Hazlewood.
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@IndyCapeSportProteas captain Faf du Plessis slammed his seventh T20 international half-century to take the Proteas to a massive 204/7 in the second clash against Australia at the Wanderers.
Original source: Faf fires Proteas to big total