Michael Cheika has opted for a new centre combination for the opening Test against England, leaving Israel Folau at full-back for the series opener.
Reds centre Samu Kerevi has been handed his Test debut, combining with Tevita Kuridrani in the midfield, in a move away from the dual playmaking structure Cheika has favoured in the past.
Folau will stay in his regular Test spot after speculation that he was set for a move into the centres.
Christian Lealiifano landed in Brisbane late on Wednesday, but ultimately time was against him in a bid for a starting spot, with the Brumbies playmaker set to come off the bench for his first Test action since 2014.
Lealiifano will play a handy back-up to fly-half Bernard Foley, with the ability to also fill the 12 spot off the pine.
Karmichael Hunt has missed the chance for a debut, after being well and truly in the mix at the selection table, along with youngster Reece Hodge, who was tipped to possibly fill a utility role off the bench.
Towering lock Rory Arnold has trained his way into a starting spot, with the 208cm second-row partnering with Rob Simmons in his Test debut, filling the void left by Kane Douglas, still on the comeback from a knee injury.
Force full-back Dane Haylett-Petty is the third debutant in the starting side, lining up on the wing for his first Wallabies opportunity, rewarded for a standout Super Rugby season.
Cheika has opted to stick with the familiar in the backrow, giving Scott Fardy, Michael Hooper and David Pocock the chance to pick up from where they left off at the World Cup.
Greg Holmes has pipped Sekope Kepu for the starting tighthead spot, just his second run-on start under Cheika after packing down against Argentina in the Rugby Championship.
Reds half-back Nick Frisby completes the roster of first-timers to run out at Suncorp, set to come off the bench for a potential Test debut in front of his home crowd.
Returned lock James Horwill has also been named in the 23, after cutting short his honeymoon to reunite with the Wallabies, paving the way for him to reignite his combination with former Reds team-mate Simmons in the second-row.
Winger Rob Horne has been elevated to the vice-captaincy for the first time, alongside Hooper, in a nod to his dedication to the Wallabies cause.
Cheika said the blend of youth and experience would re-energise the team.
"We have a good mix of new blood and players who have been connected to the group for some time and the energy and enjoyment within the group has been excellent," he explained.
"The work ethic and application of every player in the squad shows just how much the Wallabies jersey means to each of them, and these 23 players know they represent the group when they run out on Saturday.”
Australia: 15 Israel Folau, 14 Dane Haylett-Petty, 13 Tevita Kuridrani, 12 Samu Kerevi, 11 Rob Horne, 10 Bernard Foley, 9 Nick Phipps, 8 David Pocock, 7 Michael Hooper, 6 Scott Fardy, 5 Rob Simmons, 4 Rory Arnold, 3 Greg Holmes, 2 Stephen Moore (c), 1 Scott Sio
Replacements: 16 Tatafu Polota-Nau, 17 James Slipper, 18 Sekope Kepu, 19 James Horwill, 20 Dean Mumm, 21 Sean McMahon, 22 Nick Frisby, 23 Christian Lealiifano
Date: Saturday, June 11
Venue: Suncorp Stadium, Brisbane
Kick-off: 20:00 local (10:00 GMT)
Referee: Romain Poite (France)
Assistant Referees: Craig Joubert (South Africa), Glen Jackson (New Zealand)