Cooper scored a superb individual try against Gloucester on Tuesday
Australia will field an all-new centre pairing against England on Saturday in the first autumn Test at Twickenham.
With Berrick Barnes and Stirling Mortlock both injured, Quade Cooper and Digby Ioane will form the Wallabies midfield for the Cook Cup encounter.
Ioane switches to outside centre for the first time in a Test to accommodate Drew Mitchell's return on the left wing, with Cooper at inside centre.
Adam Ashley-Cooper moves to full-back and George Smith returns at open-side.
The experienced flanker will win his 107th cap on Saturday, taking over from David Pocock in the back row.
"We were looking to give George this one," Australia's assistant coach Jim Williams said. "Poe [Pocock] played outstandingly in Tokyo [the 32-19 loss to New Zealand] but we monitor well-being week to week."
Ashley-Cooper's switch sees precocious full-back James O'Connor dropping to the bench, as does centre Ryan Cross.
Ioane, 24, who returned from a shoulder injury to play against the All Blacks on the wing, will win his sixth cap alongside Queensland Reds team-mate Cooper.
Cooper, 21, has eight caps but starts only his second Test, after scoring an individual try and kicking 11 points for Australia's second-string in midweek as they opened their European tour with a 36-5 win over Gloucester.
"Tuesday was influential for us in terms of Quade's selection. He just showed how he is coming of age and he has been rewarded for that," said coach Robbie Deans.
Mitchell is also rewarded for a two-try performance at Kingsholm with a recall after being an unused replacement in Tokyo.
Saturday's match is the first of four in a row for the Wallabies against the Home Unions, with further Tests against Ireland, Scotland and Wales.
They won 28-14 at Twickenham a year ago, but only eight of the starting side that day remain, although twice as many as the England side from the same fixture.
Australia team: Adam Ashley-Cooper (Brumbies), Peter Hynes (Queensland Reds), Digby Ioane (Queensland Reds), Quade Cooper (Queensland Reds), Drew Mitchell (NSW Waratahs), Matt Giteau (Brumbies), Will Genia (Queensland Reds); Benn Robinson (NSW Waratahs), Stephen Moore (Brumbies), Ben Alexander (Brumbies), James Horwill (Queensland Reds), Mark Chisholm (Brumbies), Rocky Elsom (Brumbies, captain), George Smith (Brumbies), Wycliff Palu (NSW Waratahs).
Replacements: Tatafu Polota Nau (NSW Waratahs), Matt Dunning (Western Force), Dean Mumm (NSW Waratahs), David Pocock (Western Force), Luke Burgess (NSW Waratahs), Ryan Cross (Western Force), James O'Connor (Western Force).