Needing to achieve the highest successful chase at Newlands after Hashim Amla's 97 not out inspired South Africa to 178 for four, Australia achieved victory with four balls to spare, clinching the three-match series 2-1.
Usman Khawaja (33) and Shane Watson (42) gave Australia a strong start, putting on 76 for the first wicket in 8.2 overs.
Both fell to leg-spinner Imran Tahir in the space of three balls, but captain Steve Smith and David Warner made virtually sure of victory with a third-wicket stand of 79.
It was the last match for both teams before they leave for the World Twenty20 in India on Thursday.
Amla hit eight fours and four sixes in a 62-ball innings as South Africa posted a challenging total. It was the highest score by a South African in a Twenty20 international against Australia and the highest individual score at Newlands.
The six-over power play yielded 68 runs but the scoring rate slowed when the fielding restrictions were lifted, with leg-spinner Adam Zampa conceding only 23 runs in a four-over spell.
Zampa should have had the wicket of Rilee Rossouw, with Maxwell putting down a straightforward catch on the midwicket boundary when the batsman had made three of his eventual 16 runs.
South Africa chose to bat first on a ground where the average total for teams batting first in floodlit games was 154.
Left-arm spinner Aaron Phangiso was not included in the South African team despite having his bowling action cleared in an independent test, after failing a similar test ten days earlier.
Coach Russell Domingo said Phangiso needed more time to work on and gain confidence with the adjustments he had needed to make.
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