Made to bat first, Australia put up 226-6 then bowled out South Africa for 115 in 15.3 overs.
New captain Mitch Marsh led with a 22-ball fifty in an unbeaten 92, and was supported by Tim David's 28-ball 64.
All four debutants contributed, especially leg-spinner Tanveer Sangha with 4-31 and fast bowler Spencer Johnson's 2-33.
South Africa never got going. It was 69-5 and lost its last five wickets for nine runs.
Marsh walked in after only three deliveries and plundered 20 runs in the game's second over bowled by Lungi Ngidi.
Matthew Short went after Marco Jansen and the 50 partnership was raised in less than four overs.
Marsh hit medium-pacer Lizaad Williams out of Kingsmead in the fifth over and achieved his fastest T20 fifty — off 22 balls — in the ninth over.
David slapped Tabraiz Shamsi for sixes over long on and midwicket, and sent a delivery by new medium-pacer Gerald Coetzee over midwicket.
After his 24-ball half-century, David had one more six in him, pulling Shamsi, before he was out to a great catch by Temba Bavuma on the boundary.
David and Marsh combined for 97 runs.
Marsh was losing steam but finished unbeaten after 13 boundaries and two sixes.
South Africa's reply was a bust.
Bavuma inside-edged Marcus Stoinis on to his stumps in the first over.
Stoinis was tagged for 15 runs by Rassie van der Dussen, and new fast left-armer Johnson went for 17 straight after.
But Van der Dussen fell to Sean Abbott on 21 and Sangha's introduction decisively ended the contest.
Sangha's first over netted captain Aiden Markram, who cut straight to Stoinis at backward point.
Batting newcomer Dewald Brevis lasted six balls, hitting Sangha straight to long off. Tristan Stubbs was stumped next ball, at 69-5.
Sangha wound up with four wickets while South Africa opener Reeza Hendricks batted through for 56 off 43.
Stoinis returned with two wickets in one over, and Johnson got the last two in one over, including Hendricks.
The second T20 is on Friday.
AP cricket: https://apnews.com/hub/cricket