Australia has eased to victory in its series-opening T20 clash with South Africa thanks to some batting class from captain Alyssa Healy.

The wicketkeeper-batter was in doubt for the clash at Manuka Oval due to an illness but she proved her fitness and then carved a match-winning 46 as the hosts sealed victory with five balls and eight wickets to spare.

A tidy half-century from South African opener Tazmin Brits helped her side post 6-147 but it proved well short of a competitive total against the dominant Australians.

Star batter Beth Mooney cashed in late and finished with an unbeaten 72 to continue her strong recent form for the national team.

Healy looked in brilliant touch from the moment she took to the crease and quickly broke the back of the chase, smacking two sixes and six fours in her 46 off 28 balls.

An audacious flick over mid-wicket to cart South African bowler Marizanne Kapp for four and a massive six back over Nonkululeko Mlaba's head were eye-catching.

The partnership between the ICC's two top-ranked batters added 65 runs, Mooney playing some masterful strokes in finding 11 fours and a huge six that completed the result.

By the time Healy fell chipping Nadine de Klerk to long-on, Australia was virtually home, with Mooney and Tahlia McGrath (24) steering it to victory in the final over, while never being in any danger of losing.

It was not the start the Proteas were looking for in their multi-format series with Australia, with the sides slated for three T20s, three ODIs and a Test match during the next month.

Brits got bogged down early and could hardly find a run but came to life in the middle stages of South Africa's innings after Grace Harris's foot touched the boundary rope while trying to complete a catch.

She took that second chance and ran with it, hitting two sixes and six fours while carrying her bat through the innings as the backbone of South Africa's batting.

Sune Luus (19) worked well with Brits and hit Georgia Wareham for consecutive fours through cow-corner. However, she fell on the very next ball, Healy taking a crafty leg-side catch behind the stumps.

Australian pace bowler Darcie Brown picked up two crucial early scalps in taking 2-20, while Ellyse Perry also helped limit the South African scoring with 2-13 off her three overs.

Canberra will host the second T20 on Sunday morning before the series shifts to Hobart on Tuesday.

AAP