Gareth Anscombe comes into the side to make his first International start and he forms a new-look back three alongside Alex Cuthbert and Liam Williams.
Cuthbert will be making his 40th test appearance since making his debut against Australia back in 2011 whilst Williams returns from injury after missing the victory against Fiji.
George North is named at outside centre and he will partner Jamie Roberts for the third time in midfield.
Dan Biggar and Gareth Davies, who have collected the last two man-of-the-match awards in Wales’ victories continue their partnership at half-back.
Paul James returns from injury to start in the front row alongside hooker Scott Baldwin and prop Samson Lee.
Luke Charteris comes into the starting line-up to partner Alun Wyn Jones who makes his 99th Test appearance.
Captain Sam Warburton switches to blindside flanker and features alongside fellow British and Irish Lions Justin Tipuric and Taulupe Faletau.
“Saturday is another huge encounter and both sides will be coming in with momentum and looking to top Pool A,” said Wales Head Coach Warren Gatland.
“We have been impressed with Australia so far in this competition and we know a step up is required at Twickenham this weekend. It is still all to play for in terms of the knock-out phases.
“We’ve trained well this week, had a full squad to pick from and it is great to welcome back players from injury.”
Ken Owens, Aaron Jarvis and Tomas Francis are named as the front-row replacements with Jake Ball and Ross Moriarty completing the forward contingent. Lloyd Williams, Rhys Priestland and James Hook provide the back line cover.
WALES TEAM TO PLAY AUSTRALIA:
Gareth Anscombe (Cardiff Blues), Alex Cuthbert (Cardiff Blues), George North (Northampton Saints), Jamie Roberts (Harlequins), Liam Williams (Scarlets), Dan Biggar (Ospreys), Gareth Davies (Scarlets), Paul James (Ospreys), Scott Baldwin (Ospreys), Samson Lee (Scarlets), Luke Charteris (Racing 92), Alun Wyn Jones (Ospreys), Sam Warburton (Capt) (Cardiff Blues), Justin Tipuric (Ospreys), Taulupe Faletau (Newport Gwent Dragons).
Replacements: Ken Owens (Scarlets), Aaron Jarvis (Ospreys), Tomas Francis (Exeter Chiefs), Jake Ball (Scarlets), Ross Moriarty (Gloucester Rugby), Lloyd Williams (Cardiff Blues), Rhys Priestland (Bath Rugby), James Hook (Gloucester Rugby).