Australia stars David Pocock and Israel Folau have lost their fitness battles ahead of Sunday's World Cup quarter-final against Scotland at Twickenham.
Pocock has been ruled out by a calf problem sustained in the 15-6 victory over Wales last weekend and is replaced by Ben McCalman at number eight.
Folau suffered an ankle complaint in the same Pool A game and makes away for Kurtley Beale at full-back with Quade Cooper promoted to the bench.
Michael Hooper returns from suspension to start at openside while lock Rob Simmons is drafted into the starting XV, displacing Dean Mumm to the replacements.
Captain Stephen Moore and centre Matt Giteau will become the seventh and eighth Wallabies to make 100 international appearances when they line up against the Scots.
“Those lads don’t need to have played 100 games for Australia to have the respect from me and the other players in the team,” head Coach Michael Cheika said.
“It’s what they do in training every day, how hard they work and what they’re prepared to sacrifice that sets them apart.”
Australia thumped England by a record score at Twickenham and edged Wales at the same venue, but Cheika insists Scotland will be the Wallabies’ most dangerous foes yet.
“This will be the most difficult game we play and that’s not disrespecting our other opponents at all because every match has been tough, but this will be the toughest,” Cheika said.
“There’s going to be a lot of pain, it’s going to be physical and I want the players to enjoy that as well because that’s when it’s worth it.
“Guarding against complacency is pretty easy because we don’t think we are complacent.
“We’re acutely aware that this is really important for our own journey as a team.
“I’ve seen a lot of the Scottish players saying they can win — and they can, they can.
“It’s the reality of sport and what we need to make sure is that our mindset is really clear on what we’re prepared to do to get that victory.”
Australia: K Beale, A Ashley-Cooper, T Kuridrani, M Giteau, D Mitchell; B Foley, W Genia; S Sio, S Moore (captain), S Kepu, K Douglas, R Simmons, S Fardy, M Hooper, B McCalman
Replacements: T Polota-Nau, J Slipper, G Holmes, D Mumm, S McMahon, N Phipps, M Toomua, Q Cooper.
