Wilkinson, England's 2003 World Cup final match-winner, has been ruled out of the opening game against the USA in Lens on Saturday.
Bath's Olly Barkley will wear the number 10 shirt, with Andy Farrell lining up on the bench.
Wilkinson will undergo a scan later on Tuesday, but England are issuing no further medical bulletins at this stage.
Wasps star Josh Lewsey will win his 50th cap. He lines up in a team showing six changes from England's final tournament warm-up Test against France in Marseille just over two weeks ago.
England head coach Brian Ashton has also found room for Lawrence Dallaglio, who starts in an all-Wasps back row alongside Joe Worsley and Tom Rees.
Dallaglio, veteran of 80 caps, starts ahead of Nick Easter, who failed to feature in the match-day 22.
Worsley, meanwhile, plays at blind side flanker, while Leicester's Martin Corry, who has recovered from a knee problem, has to be content with a place on the bench.
Elsewhere, Jamie Noon and Mike Catt form the centre combination - Dan Hipkiss misses out - and fit-again Andrew Sheridan returns to the front row in place of Perry Freshwater.
England's poor lineout performance in Marseille has undoubtedly cost Bath skipper Steve Borthwick a World Cup start, with Leicester's Ben Kay preferred in the second row alongside Simon Shaw.
London Irish scrum half Peter Richards, whose recovery from back trouble was only confirmed late last week, gains an immediate opportunity to impress off the bench, understudying for Shaun Perry ahead of Andy Gomarsall.
Despite England's dismal run of form since they won the World Cup in Australia four years ago, they will be expected to start their 2007 campaign with a points blitz against vastly inferior opponents.
Ashton will demand a display bristling with confidence and creativity as England look to start in style ahead of their crunch pool encounter with South Africa in Paris on Friday week.
Ashton's first tournament selection suggests the likes of Farrell, Easter and Borthwick could struggle to make an impression on the competition.
Big-money rugby league recruit Farrell has endured a difficult beginning to his union career, and it now looks as if he will only have a bit part role to play, especially if Catt remains fit.