Australia whitewashed by Proteas despite Labuschagne's maiden ODI century
Labuschagne scored 108 out of the tourists' 254-7, bouncing back from a duck in Bloemfontein last time out to reach three figures in Potchefstroom, which is around 40 minutes away from where the batsman grew up before moving Down Under.
Anrich Nortje (2-35) and JJ Smuts (2-42) had kept Australia to a below-par total which never looked like being enough given neither Mitchell Starc nor Pat Cummins were in their attack.
Smuts (84), Kyle Verreynne (50) and the in-form Heinrich Klaasen (68 not out) all registered half-centuries as South Africa claimed a six-wicket win with 27 balls to spare, sealing a 3-0 series victory.
South Africa made a strong start when opener David Warner nicked behind off Nortje on just four and Steve Smith was pinned lbw by Andile Phehlukwayo, the decision remaining with the umpire's call following a review.
The pressure was perhaps telling on Australia captain Aaron Finch, who tore into Labuschagne for turning down a single from the non-striker's end following a brilliant piece of fielding from David Miller.
There was more great work from Miller at short extra cover to remove Finch on 22 as the fielder got his fingers underneath a low chance to give Daryn Dupavillon a maiden ODI wicket.
D’Arcy Short (36) put on 81 alongside Labuschagne before becoming Smuts' first victim and Mitchell Marsh (32) was sent back thanks to more brilliance from Miller, who dived to stop Labuschagne's drive and whipped an underarm throw to wicketkeeper Quinton de Kock for a simple run out.
Alex Carey was bowled by Smuts in the same over without scoring but Labuschagne went on to make an emotional century in front of around 50 watching family members.
In reply, South Africa lost both openers to Josh Hazlewood but the lack of Starc, who has returned home to watch wife Alyssa Healy in the Women's T20 World Cup final, and Cummins allowed Smuts and Verreynne to put on 96 for the third wicket.
Both men picked out fielders from mistimed slogs, but Warner was then unable to hang on to a loose shot from Klaasen, who reached his 50 when shelled at mid-on.
Klaasen sealed the victory by going four-four-six off Marsh, taking his tally for the series to 242 runs.