The returning David Pocock was Australia's match-winner as they handed Ireland a first defeat in over a year with an 18-9 victory in the first Test in Brisbane.
Ireland have never previously played a three-Test series in Australia and they rested several of their Leinster contingent for the opener at Suncorp Stadium after the province's exploits in the Pro14 and European Champions Cup finals.
Johnny Sexton, Tadhg Furlong and Cian Healy were left on the bench while Garry Ringrose and Dan Leavy were not selected at all, but the second-ranked side in the world were still competitive and led until the final 10 minutes.
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Australia, having earlier seen an Israel Folau try disallowed, upped the ante in the closing stages and Bernard Foley put them 11-9 to the good with a penalty before Pocock, playing his first international since taking a sabbatical from the game last year, crossed from close range to hand Ireland a first loss since a 22-9 reverse at the hands of Wales in March 2017.
Foley booted Australia into a third-minute lead after Bundee Aki was pinned for offside, but the Wallabies fly-half was penalised for the same offence 11 minutes later and Joey Carbery levelled matters.
Jacob Stockdale produced defensive heroics to preserve parity as he somehow caught Marika Koroibete and tackled the wing into touch after he looked certain to score.
Carbery slotted over a second three-pointer from in front of the posts to give Ireland the lead but, though the tourists had looked menacing in attack, it was the Wallabies who crossed for the first try as Will Genia sent Foley over in the corner after Pocock had won a loose ball.
Australia's slim lead looked poised to only last a minute after the restart when CJ Stander burst through the Wallabies' defence, but Dane Haylett-Petty and Koroibete managed to catch the number eight and hold him up over the line.
The boot of Carbery did eventually put Ireland back in front, yet they were grateful to the TMO for keeping them ahead as the officials attracted the ire of the Brisbane crowd.
Folau raced over wide on the right following slick handling from Australia after Aki had been turned over, but the TMO went back several phases to chalk off the score for a tackle on a player without the ball.
Despite that misfortune, Australia finished the stronger of the two sides, excellent work at the scrum deep in Ireland territory earning them a penalty that Foley easily converted to swing the pendulum back in their favour.
Stockdale was then penalised close to his own line as Australia were rewarded for excellent pursuit of a kick downfield, and they swiftly took advantage as Pocock bundled his way over.
72 | DAVID POCOCK!
— Qantas Wallabies (@qantaswallabies) June 9, 2018
Poey caps off a sensational #Wallabies return with a pick and go try. We lead 16-9. #AUSvIRL #GoldBlooded
Kieran Marmion appeared to have crossed for a late consolation for Ireland but that was disallowed for a knock-on, leaving the tourists with plenty of work to do ahead of the second Test in Melbourne next week.