Concussion substitute Labuschagne knocks out South Africa
Labuschagne replaced Cameron Green, hit on the head by a rising delivery from Kagiso Rabada, and made a match-winning 80 not out to see Australia to their target after putting South Africa into bat and dismissing them for 222.
Australia, who secured victory with nine overs to spare, had been in serious trouble at 113-7 as they plundered early runs but also lost a steady stream of wickets.
Labuschagne was the first ever test concussion substitute at Lord's in the 2019 Ashes, when he replaced Steve Smith and made 59, and looked at ease when he took over from Green.
Labuschagne’s unbeaten 112-run eighth-wicket partnership with Ashton Agar guided Australia to victory in the first game of the five-match series and reminded the Australian selectors, who left him out of the World Cup squad, of his prowess.
His innings squeezed the energy out of an excited home attack, who had early inroads as they looked to defend a modest total. Agar contributed 48 not out.
Earlier, South Africa captain Temba Bavuma finished on 114 not out to become only the second South African to carry his bat through an ODI innings.
Opener Quinton de Kock and big hitters Aiden Markram, Heinrich Klaasen and David Miller all failed to get going with the destructive Miller out second ball with an edge to wicketkeeper Alex Carey off Josh Hazelwood, who took 3-41.
All-rounder Marco Jansen helped Bavuma steady the innings in a 57-run sixth-wicket partnership before he was bowled by Hazelwood for 32.