Jake Weatherald will join fast bowler Brendan Doggett in debuting for Australia in the Ashes opener in Perth.
While Doggett was a near-certainty to play after Josh Hazlewood was ruled out due to a hamstring injury, Australia were weighing up whether to pick Weatherald or use Marnus Labuschagne at the top.
But the Northern Territory-raised Weatherald will become Khawaja's sixth opening partner since David Warner retired from Test cricket in January 2024.
"He's got a lot of courage," stand-in Australia captain Steve Smith said of Weatherald.
"He wants to face bowlers (in the nets) the entire time.
"The guys were charging in, bowling fast and he took it on. He was getting in really good positions, and he goes about it a certain way.
"He's been selected for his performances over the last 18 months, in particular, he's batted exceptionally well at the top of the order for Tasmania.
"Hopefully he can bring that to the Test arena."
It means Weatherald's Tasmania teammate Beau Webster misses out, dropped after playing seven Tests since his remarkable debut against India in January.
"(Webster) came into international cricket and lit it up immediately," Smith said.
"It's a really tough one on him."
It will be the first time since Kurtis Patterson and Jhye Richardson came in to face Sri Lanka in January 2019 that Australia have blooded two debutants in the same Test.
After being dropped for the tour of the Caribbean following a lean run, Labuschagne is back following his outstanding start to the summer for Queensland.
"Marnus when he's batting at his best at No.3, he makes us a very good cricket side," Smith said.
"We couldn't really leave him out after he came back and did exactly what was told of him."
Cameron Green, who had pushed up to No.3 since his return from a serious back injury, will go back to No.6 where he started his Test career.
But Green looms as Australia's long-term No.4 when Smith ends his illustrious Test career in coming years.
The 26-year-old has only just returned to bowling after playing as a batter-only in his four Tests this year.
England on Wednesday named a 12-man squad for the first Test, picking both speedsters Jofra Archer and Mark Wood as they aim to capitalise on a traditional pacy and bouncy pitch in Perth.
With England training on Thursday afternoon, captain Ben Stokes and coach Brendon McCullum will decide who they leave out for the start of what shapes as the closest Ashes series in Australia for more than 40 years.
Stokes had no concerns over picking Wood, who suffered hamstring tightness in England's warm-up game on the weekend and hasn't played a competitive match since February.
England are seeking to win an away Ashes Test for the first time since they last won a series back in 2010-11.
Australia have destroyed England during the past three home Ashes, winning 5-0, 4-0, and 4-0.
But with the latest evolution of Bazball, England are believing they can create history, starting an Ashes in Perth for the first time since 1982.
"We've obviously come here with the goal, and that goal was to get on that plane this January and return to England as Ashes winners," Stokes said.
"But we know it's going to be very, very tough."
AUSTRALIA XI: Jake Weatherald, Usman Khawaja, Marnus Labuschagne, Steve Smith (capt), Travis Head, Cameron Green, Alex Carey, Mitchell Starc, Nathan Lyon, Scott Boland, Brendan Doggett.
ENGLAND SQUAD: Zak Crawley, Ben Duckett, Ollie Pope, Joe Root, Harry Brook, Ben Stokes (capt), Jamie Smith, Gus Atkinson, Mark Wood, Jofra Archer, Shoaib Bashir, Brydon Carse.
