Kyle Abbott led what was effectively South Africa's back-up bowling attack as Australia were bowled out for 167, the lowest total of the series.
South African captain Faf du Plessis made 69 as South Africa secured their fourth successive win with 14.3 overs to spare.
It left Australian captain Steve Smith having to contemplate the prospect of a 5-0 series defeat going into the final match in Cape Town on Wednesday.
Smith said he was disappointed with the batting performance.
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"The wicket maybe wasn't as good as the others but 250 was about par."
Having clinched the five-match series by winning the first three games, South Africa rested fast bowlers Dale Steyn and Kagiso Rabada and leading spin bowler Imran Tahir.
They were replaced by Abbott and spinners Tabraiz Shamsi and Aaron Phangiso.
Man of the match Abbott admitted that he felt nervous before the game, having not been part of the first three matches.
But he bowled both Australian opening batsmen inside the first three overs and finished with four for 40. Unorthodox left-arm wrist spinner Tabraiz Shamsi took three for 36 and orthodox left-armer Phangiso picked up the last two wickets at a cost of 17 runs.
He bowled Aaron Finch with the third ball of the match and then bowled David Warner with the first ball of his second over. He struck another crucial blow when he was brought back into the attack and had Mitchell Marsh caught behind for 50, ending a 62-run sixth wicket partnership with Matthew Wade.
George Bailey was leg before wicket to Dwaine Pretorius as Australia slumped to 12 for three.
It became 49 for five when Shamsi deceived Australian captain Steve Smith and Travis Head, trapping them both leg before, in the space of three balls.
Tremain, who took some heavy punishment in his first two matches for Australia earlier in the series, gave South Africa some early worries by dismissing both opening batsmen, Hashim Amla and Quinton de Kock.
With a strong wind blowing across the field, Du Plessis survived a chance on 16 when Adam Zampa misjudged a high catch off John Hastings at point.
He shared half-century partnerships with JP Duminy and Rilee Rossouw before holing out to deep square leg off Marsh's bowling. He hit eight fours in an 87-ball innings.
- Streaky Williamson -
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Williamson has survived four chances in his innings. Maharaj found an edge when he was on 10 and again on 40, but both fell fractionally short of Hashim Amla at first slip.
On 72, he was sent back by Henry Nicholls and he made his ground by the slimmest of margins, before an edge off Philander four runs later failed to carry to the slip cordon.
The Maharaj-Amla partnership made no mistake when removing Nicholls for 12, with Amla diving to his left to take a sharp one-handed catch.
It was the beginning of the end for South Africa as Quinton de Kock fell for 10 to his nemesis Patel, dismissed by the off-spinner for the third time in as many innings on this tour.
Patel also bowled Kagiso Rabada while Trent Boult claimed Bavuma for 64, Maharaj for five and finished the innings bowling Philander for 21.
Boult was the sharpest of the New Zealand bowlers with four for 64, while Wagner took three for 88 and Patel finished with 2-85.