Paceman Michael Neser was superb for Australia on day four, dismissing danger men Ben Stokes (50) and Will Jacks (41) after they'd kept England's hopes of victory alive.
Neser (5-42), a controversial selection ahead of Nathan Lyon as Australian went in without a full time spinner, produced a maiden Test five-wicket haul in his first match in the baggy green since 2022.
With England all out for 241 in their second dig, Australia were left chasing 65 runs for victory under lights in the day-night fixture.
Gus Atkinson (2-37) struck twice to bowl swashbuckling Travis Head (22 runs off 22 balls) and send Marnus Labuschagne (3) packing caught behind.
But the chase was never in serious doubt and Steve Smith (23no off nine balls) hit a six to win the game as Australia finished on 2-69 in the 10th over of the innings.
"The adrenaline was pumping at the end there," said Smith, who exchanged words with England's Jofra Archer in the dying overs regarding the quick's express pace.
Australia are now in the box seat to retain the urn for a fifth consecutive Ashes as the series moves to Adelaide for the third Test from December 17.
"It's been a wonderful couple of weeks for the team. I think we've played some sensational cricket," Smith said.
"We've identified moments in the game and made the most of them."
A first Test century in Australia for Joe Root (138no) was a highlight for England in Brisbane, but the tourists have now been left needing to defy history in pursuit of the urn.
No England side has recovered from 2-0 down to win a five-Test Ashes series, but captain Stokes is remaining defiant.
"The worst thing to do now is to not have hopes, and not realise that we've still got that opportunity to do what we came out here to do," he said.
"We are 2-0 down, there is three games left. If we lose hope over the next couple of weeks, or even next week, we might as well not turn up."
Earlier in the match, Mitchell Starc continued his blistering series by top-scoring with 77 runs to help Australia post a massive first-innings total of 511.
He was by far Australia's best bowler in the first innings with figures of 6-75, took the key wicket of Root as England wobbled in their second stay at the crease, and was deservedly named player of the match.
But Neser was Australia's key man on Sunday, finally snapping a disciplined 96-run stand between Jacks and Stokes for the hosts' first scalp in the 35th over of day four.
He saw off new inclusion Jacks thanks to a freakish one-handed slips catch from a diving Smith.
Stokes had led the way for England and batted patiently for his 50th Test half-century before an outside edge sailed into Alex Carey's gloves off the bowling of Neser. He made 50 from 152 balls.
Stokes literally broke his bat attempting to lift England back into the game.Â
He needed a new willow after driving Brendan Doggett (1-56) to cover midway through the session.
Stokes withstood the pain of wearing a Neser delivery in the most sensitive of areas before raising his half-century with a single to point.
The touring fans gave Stokes a standing ovation, but he lasted only one more over before Neser struck.
Skipper Stokes knew the significance of his wicket, striking at his own helmet in anger as England's hopes of setting a defendable target left the pitch with him.
Right-arm paceman Neser had his first Test five-for when Brydon Carse (7) clipped him to Smith just after 6pm local time, completing an English collapse of 4-17.
The tourists were also left to rue a 6-80 collapse under lights on day three that had meant even taking the lead on day four was an uphill battle.
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