South Africa triumphed by 12 runs after scoring 4-158 led by new captain Quinten de Kock’s 70 from 47 balls, with Australia falling short at 6-146 in reply.
David Warner worked hard for the tourists with an unbeaten 67* from 56 deliveries but middle-order wickets fell regularly in the final five overs as Lundi Ngidi (3-41) did damage.
Australia needed 37 runs from 29 balls when Alex Carey landed a major blow with a maximum from the first ball in the 16th over, but the visitors fell apart.
Carey, elevated to four to negate spinner Tabraiz Shamsi, lost his wicket that over, before Mitchell Marsh combined with Warner to put Australia back in control, needing only 25 from 18.
But Marsh and Matthew Wade fell in quick succession, before Ashton Agar had a nightmare, with Kagiso Rabada conceding only three runs in the penultimate over. Australia couldn’t get close in the final over, going down by 12 runs.
Australia captain Aaron Finch said: “I thought we were in the hunt for most of the chase. We just didn’t get that kick at the end that we needed.
“It was a good contest. David didn’t get quite as much of the strike as he would have liked at the end.
“Both teams bowled well at the end, not ideal but a great game still. Our middle order are trying to get a bit more time there… it would have been nice for them to get that winning feeling.”
Australia assistant coach Andrew McDonald added: “We saw at the Wanderers the other day that they had some work to do and they were able to do that, batting first.
“Clearly batting second on a tiring surface is a totally different situation. They’ll be no doubt better for that experience as we grow and build towards the T20 World Cup.”
The two sides will meet again in the third and final T20I in Cape Town on Wednesday with the series locked at 1-1.