Jason Robinson will become the first former rugby league player to lead England after being named captain for Saturday's Test against Canada.
The Sale Sharks skipper takes over from the injured Jonny Wilkinson.
Sharks team-mate Mark Cueto will win his first cap on the right wing with Josh Lewsey switched to the left flank.
Henry Paul is handed his first start in the centre, Charlie Hodgson and Andy Gomarsall are the half-backs and Steve Borthwick starts in the second row.
"Jason is an outstanding member of the England team who has led by example for the three years he has been playing international rugby union," said England coach Andy Robinson.
"He has an exceptional record not only in this sport but also in rugby league, earning him the respect of the whole squad.
"This season he is captain of Sale Sharks and doing a fantastic job and I have no hesitation in offering him the captaincy in Jonny's absence.
"I have no doubt others could also have stepped up to the mark but I am very satisfied Jason will do well in the role."
Robinson, who is the first black player to lead England, said being named captain is one of the highlights of his glittering career.
"It's not something I have deliberately sought with England or Sale but I am enjoying being captain at my club and am understandably excited at the prospect of being England captain at Twickenham on Saturday," he said.
Robinson, who has scored 19 tries in 33 Tests, will have Mike Tindall as his vice-captain, a position he held during the summer tour to New Zealand and Australia.
Cueto gets his chance after proving himself one of the best finishers in the Zurich Premiership, with 39 tries in 71 outings.
Paul, meanwhile, will win his fourth cap after three appearances as a replacement in the past three seasons.
Three other players - Sale prop Andrew Sheridan, Gloucester flanker Andy Hazell and Newcastle scrum-half Hall Charlton - could win their first caps off the bench.
Charlton benefits from the unavailability of Leicester scrum-half Harry Ellis, who has an Achilles tendon injury.
Gomarsall has been named to start at scrum-half, providing he can shake off a back problem, with Matt Dawson poised to join the squad if not.
In all there are nine changes, including Lewsey's positional switch from full-back to left wing, following England's last game - a 51-15 defeat to Australia in June.
But only four players - Robinson, Lewsey, Tindall and hooker Steve Thompson - remain from England's World Cup final side.
Three more - wing Ben Cohen, centre Will Greenwood and lock Ben Kay - are among the replacements.
In the pack, experienced Leicester prop Graham Rowntree is recalled for his
first England appearance since a World Cup warm-up game against France 14 months ago.
Bath lock Danny Grewcock wins his 50th cap while Leicester flanker Lewis Moody returns after a 10-month injury absence for his first cap since the World Cup final.
Martin Corry gets the nod at number eight after the retirement of former captain Lawrence Dallaglio.
England team: Jason Robinson, (Sale Sharks - capt); Mark Cueto (Sale), Mike Tindall (Bath - vice captain), Henry Paul (Gloucester), Josh Lewsey (Wasps), Charlie Hodgson (Sale), Andy Gomarsall, (Gloucester); Graham Rowntree, (Leicester), Steve Thompson (Northampton), Julian White (Leicester), Danny Grewcock (Bath), Steve Borthwick (Bath), Joe Worsley (Wasps), Lewis Moody (Leicester), Martin Corry (Leicester).
Replacements: Andy Titterrell (Sale), Andrew Sheridan (Sale), Ben Kay (Leicester), Andy Hazell (Gloucester), Hall Charlton (Newcastle), Will Greenwood (Harlequins), Ben Cohen (Northampton).