After being crushed by 98 runs in Cairns on Tuesday night, Australia again struggled batting under lights as the recent 50-over retirements of Steve Smith and Glenn Maxwell were laid bare.
Chasing South Africa's 278, Australia's only hope was Josh Inglis as their white-ball keeper made batting look easy in comparison to the rest of the line-up.
But when in sight of his second ODI century, Inglis (87 from 74 balls) went for a wild shot and was caught behind off Lungi Ngidi.
Once the 30-year-old was dismissed, Australia's chances disappeared as they lost 4-9 to end their innings in the 38th over.
Quick Ngidi starred in the absence of injured spearhead Kagiso Rabada, claiming 5-42 for the second five-wicket haul of his ODI career.
Australia have won just one ODI since last November - a victory over England in this year's Champions Trophy - and suffering multiple defeats to Pakistan, Sri Lanka, and now South Africa.
Marnus Labuschagne might have grabbed valuable lower-order wickets, but his spot at No.3 has to be in jeopardy.
Already dropped from the Test side, Labuschagne (2-19) gained some much-needed confidence with the ball, but it didn't translate with the bat as he was out for one after making the same score in game one.
The Proteas, who chose to bat first, appeared to be cruising to a total above 300, but were tied down late in their innings and bowled out with five balls to spare.
Labuschagne was joined by recalled quick Xavier Bartlett and fellow seamer Nathan Ellis in taking two wickets each.
Adam Zampa ensured half of the wickets were taken by spinners when he took the final scalp, after previously dismissing Tristan Stubbs and Tony de Zorzi.
Matthew Breetzke (88) and Stubbs (74) threatened to take the innings away from Australia in their 89-run stand, before the former skied an Ellis delivery to Alex Carey without the gloves in the deep.
Ellis also claimed the crucial wicket of young gun Dewald Brevis, who lit up the recent T20 series.
Captain Bavuma was rested, replaced by Tony de Zorzi, as South Africa manage his workload after badly hurting his hamstring in the World Test Championship (WTC) final in June.
Tuesday night's match was Bavuma's first in any format since lifting the WTC mace by defeating Australia at Lord's.
South Africa will be out to make it a 3-0 clean-sweep in Sunday's series finale back in Mackay.
