The Lions established early dominance, scoring tries through Sione Tuipulotu, Tom Curry, and Dan Sheehan, despite some handling errors.
Australia, appearing understrength and underprepared, mounted a second-half comeback with tries from Max Jorgensen, Carlo Tizzano, and Tate McDermott, but it was insufficient to overturn the deficit.
Key Lions players, including flankers Tom Curry and Tadhg Beirne, and the front row, were instrumental in their strong performance.
The victory marks the Lions' continued unbeaten record in Brisbane, with a large contingent of travelling fans creating a "Sea of Red" at the stadium.