The 30-year-old flyhalf will be reunited with Steve Thompson, who has made a remarkable return from injury, for the first time since they led England to the 2003 World Cup title.
"It's good to have that experience among some of the younger guys," said England manager Martin Johnson, who captained the team that beat Australia in the 2003 final.
Johnson will be relying on their experience after losing 11 of his initial 32-man squad to injury, including seven probable starters.
Wilkinson's career has been ravaged by injuries since kicking England to the world title against Australia, but is set to start under Johnson for the first time after being revitalized this season following a move to French club Toulon.
"His leadership in the group has been fantastic, his communication with the players, and particularly the younger guys, and what he brings," Johnson said. "These guys have seen what he has done over the last 10 years playing for England and it's a tremendous amount."
The 31-year-old Thompson retired in 2007 after neck surgery, but returned to action later the same year after receiving new medical advice from American and French experts.
"My whole reason for coming back was to try to play for England again," said Thompson, who had to return his compensation cash. "I've lost money from coming back but I don't regret it. I still had more in me and I wanted to do it. You have to aim to play at the highest level or there's no point coming back.
"I am really excited and I am nervous. It's like winning your first cap again really."
The Brive hooker made a brief cameo as a substitute in England's match against Argentina in June, but is now in line to make his first international start since 2006.
"It is some comeback," Johnson said. "He did retire from the game and partly realized what he was missing and had the desire to come back.
"He has got himself into shape and has played pretty well and worked very hard. He has been fantastic with us this last 10 days, as he was in the summer."
Thompson will pack down with Tim Payne at loosehead and promising Bath tighthead David Wilson, who is making just his third appearance. Louis Deacon partners captain Steve Borthwick in the second row, with Lewis Moody, Tom Croft and Jordan Crane making up the back row.
Matt Banahan and Mark Cueto start on the wings, with Ugo Monye shifting to fullback and Shane Geraghty returning at inside center alongside Dan Hipkiss.
Biarritz center Ayoola Erinle and Northampton lock Courtney Lawes are both set to make their test debuts from the bench.
Australia began the European leg of its tour by beating Gloucester 36-5 at Kingsholm on Tuesday.
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England team: Ugo Monye, Mark Cueto, Dan Hipkiss, Shane Geraghty, Matt Banahan, Jonny Wilkinson, Danny Care; Tim Payne, Steve Thompson, David Wilson, Louis Deacon, Steve Borthwick, Tom Croft, Lewis Moody, Jordan Crane.
Replacements: Dylan Hartley, Duncan Bell, Courtney Lawes, James Haskell, Paul Hodgson, Andy Goode, Ayoola Erinle.
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