Ponting was joined at the crease in the third over by his successor as captain Michael Clarke, and the pair set up Australia for a large total with a second-wicket stand of 102 off 112 deliveries.
They were in full flow, having taken the score to 96 for one after 19 overs, when rain interrupted play for four-and-a-half hours. When they returned, they had just 10 overs remaining to bat.
Clarke was unfortunate to be run out for 44 at the non-striker's end when Johan Botha deflected a fierce straight hit from Ponting into the stumps, and the same player took a fine diving catch at backward point to remove Ponting off the bowling of Dale Steyn.
It took a bullish innings of 30 not out off 21 balls from Mike Hussey to stretch Australia's total, with the Duckworth/Lewis method further adjusting it to 222.
South Africa were in trouble from the outset as left-arm paceman Doug Bollinger swung a delivery into Graeme Smith's pads and trapped him lbw in the first over.
New captain Hashim Amla looked in fine touch as he scored 24 and he steadied the innings with Jacques Kallis.
It was 18-year-old fast bowler Pat Cummins who changed the game, with two wickets in the eighth over.
Kallis, on 15, became the debutant's first ODI wicket, dragging a flatfooted drive back into his stumps, and JP Duminy (4) was then snapped up at second slip by Clarke, the left-hander deceived by a fine delivery.
Wicketkeeper Brad Haddin then took an excellent catch to remove Amla off the bowling of all-rounder Mitchell Marsh.
Controversial selections David Miller and Mark Boucher, both returning after missing the World Cup, fell cheaply to left-arm spinner Xavier Doherty, who impressed with two for 33 in six overs.
Faf du Plessis scored 27 and Botha was once again defiant in the lower-order with 25, but South Africa were bowled out for 129 and seem to be badly missing injured batsman AB de Villiers.
Johnson was the best of the bowlers with three for 20 in five overs, with Cummins providing fiery back-up for the left-armer with three for 28 in three overs.