Australia has sealed victory in the best-of-three one-day international series against South Africa, avenging its upset loss in match two with a rain-affected 110-run triumph at North Sydney Oval.

After winning the toss on Saturday, captain Alyssa Healy (60) laid the groundwork for the hosts' 9-277 before slow-starting Beth Mooney fired to 82 not out.

The pair's efforts left the Proteas requiring their largest-ever successful run chase to repeat Wednesday's surprise victory and seal a fairytale series win.

Without fellow opening bowler Megan Schutt, who was missing for personal reasons, Kim Garth (3-14) had an early breakthrough dismissing out-of-sorts Proteas captain Laura Wolvaardt (3) caught behind.

In her first over, Tahlia McGrath enticed Tazmin Brits, the only batter who had made a start to that point, into holing out to deep midwicket where she was caught for 31.

McGrath (3-23) then gave Marizanne Kapp the same treatment, the architect of Wednesday's upset win going for a fourth-ball duck after finding Darcie Brown in the deep.

South Africa had slumped to 4-63 when rain stopped play after 14 overs, and it was left to chase a revised total of 238 from 31 overs when the match resumed more than 90 minutes later.

Legspinner Alana King (4-26) wreaked havoc after the restart, exposing the visitors' lack of batting depth with career-best ODI figures.

After she dispatched Sinalo Jafta and Masabata Klaas, each without scoring, King came within inches of a hat-trick, but the ball bounced just wide of off-stump and spared Ayanda Hlubi.

But South Africa nevertheless lost 4-0 and was all out for 127 in the 25th over when Garth bowled Hlubi.

The win puts Australia back in control of the multi-format series ahead of next week's one-off Test match in Perth.

To draw the series on points aggregate South Africa need to win that match.

In Australia's innings, Healy rode her luck after being dropped on 31 at deep backward square leg by Anneke Bosch, who had two other possible catches fall at her feet on a day of mixed fielding for the tourists.

Healy notched her 17th ODI half-century with back-to-back fours straight down the ground off Nadine de Klerk, before being caught at much the same place Bosch dropped her.

When Healy went, McGrath (44) reignited the hosts by hitting young quick Hlubi (0-41) for five consecutive fours but misplayed Chloe Tryon the next over and lost her middle stump.

With a single to mid-wicket in the 43rd over, slow-and-steady Mooney brought up her 16th half-century before a patient knock began to switch gears.

A scoop shot that bounced to the boundary off Kapp was the most memorable of Mooney's 10 fours.

After belting quick Klaas for consecutive sixes, King (17) kept the strike late and Mooney's ton eluded her.

Klaas (4-56) took career-best ODI figures, and threatened to trigger another top-order collapse when Litchfield hit her to Brits at cover in the sixth over.

She dispatched Ellyse Perry (24) with an inswinger that collected middle stump and broke her 82-run partnership with Healy.

Klaas restricted Australia to four runs in the final over and tempted King into holing out to the deep.

AAP