Australia dominated all three games against a depleted home side on the small Kingsmead ground, and were the better side with bat, ball and in the field, where South Africa were sloppy.
The hosts elected to bat first and posted 190 for eight in their 20 overs, their highest score of the series but not enough as Australia easily chased down the target with 13 balls remaining.
The teams start a five-match One-Day International series on Thursday in Bloemfontein, which will serve as preparation for the Cricket World Cup in India that gets underway on October 5th.
"We had a great team effort this tour, we prepared well and took the game on," new Australia T20 captain Mitch Marsh said at the post-match presentation.
"We are building towards next year’s (T20) World Cup and I am really pleased with the players who have come into the team and stepped up."
Debutant middle-order batsman Donovan Ferreira top-scored for South Africa with 48 from 21 balls before he was run out trying to pinch the strike in the final over.
Others to get starts but not go on to big scores were opener Reeza Hendricks with 42 from 30 deliveries, and captain Aiden Markram, who crashed 41 from 23 balls.
Seamer Sean Abbott was the pick of the visiting bowlers with career-best figures of 4-31.
The home side had hope when they reduced Australia to 43 for two in the fifth over, but the visitors were able to keep up with the run-rate throughout and never looked troubled.
The excellent Head and Josh Inglis put on 85 in 42 balls for the third wicket, with the latter contributing 42 in 22 deliveries to take the game away from South Africa.
"We were slightly better today, still not where we want to be, but on an upward curve," Markram said.
"The ODI series will be important for us ahead of the World Cup, to work on combinations and get our best team out on the park."
