Owen Farrell will start at fly-half for England in Saturday's RBS 6 Nations game against Wales after Charlie Hodgson failed to recover from a finger injury.
Farrell's switch from inside centre has opened the way for Manu Tuilagi to return to the England midfield alongside Brad Barritt, one of four changes from the 19-15 win against Italy two weekends ago.
Scarlets number eight Ben Morgan, Northampton scrum-half Lee Dickson and Leicester lock Geoff Parling will all make their first Test starts for England.
Hodgson, who suffered a cut and sprain to his left index finger in training earlier in the week, was finally ruled out of the match this morning.
Farrell has been preferred at fly-half to Toby Flood, who returns to the England squad on the bench alongside fit-again Northampton lock Courtney Lawes.
"Charlie cut his finger in training earlier in the week and needed stitches but it swelled up and there is a sprain there," said England interim coach Stuart Lancaster.
"We assessed him this morning and he cannot grip fully. Owen has trained throughout and knows our patterns and plays so we are fully confident in his ability to run the game from 10.
"We are looking forward to seeing how Brad and Manu gel together in the centre.
"It's been a good start with two wins but we've got real competition for places and Lee, Ben and Geoff deserve an opportunity to start this game."
Leicester scrum-half Ben Youngs and Northampton number eight Phil Dowson drop to the bench, but there is no place for Stade Francais lock Tom Palmer, who started England's wins against Scotland and Italy.
Tuilagi's promotion into the starting line-up following Hodgson's injury has led to Harlequins full-back Mike Brown being recalled from club duty to start on the bench.
Dickson has been charged with injecting some energy and tempo at scrum half and Morgan will look to carry England over the advantage line.
Both men made a game-changing impact for England at the Stadio Olimpico, while Parling's lineout qualities have impressed the England management.
"It's been a good start with two wins but we've got real competition for places and Lee, Ben and Geoff deserve an opportunity to start this game," Lancaster said.
"It means that Phil and Ben will provide a different role from the bench and it's great to have Courtney and Toby, who can also give us options in what I am sure will be a full-on encounter.
"It's our first home game of the Six Nations which we are really excited about and we are sure the crowd will get behind us just as the travelling supporters have done in Scotland and Italy.
"Playing at Twickenham makes it extra special for us and I know we will get all the encouragement we need."
England team to play Wales in the RBS 6 Nations championship at Twickenham on Saturday, February 25 (kick-off 1600):
B Foden (Northampton Saints); C Ashton (Northampton Saints), M Tuilagi (Leicester Tigers), B Barritt (Saracens), D Strettle (Saracens); O Farrell (Saracens), L Dickson (Northampton Saints); A Corbisiero (London Irish), D Hartley (Northampton Saints), D Cole (Leicester Tigers), M Botha (Saracens), G Parling (Leicester Tigers), T Croft (Leicester Tigers), C Robshaw (Harlequins, capt), B Morgan (Scarlets)
Replacements: R Webber (London Wasps), M Stevens (Saracens), C Lawes (Northampton Saints), P Dowson (Northampton Saints), B Youngs (Leicester Tigers), T Flood (Leicester Tigers), M Brown (Harlequins)