Leicester centre Dan Hipkiss will make his England debut in Saturday's Test against Wales, while Lawrence Dallaglio is named among the replacements.
Hipkiss will partner Andy Farrell in midfield at Twickenham
Joe Worsley has been moved to open-side flanker, with Martin Corry on the blind-side and Nick Easter completing the back row.
Andy Farrell returns at inside centre in a new-look pairing with Hipkiss.
Veteran Mark Regan starts ahead of George Chuter at hooker, and Andrew Sheridan starts at prop.
England coach Brian Ashton said Regan's selection was a direct result of his impressive displays in adversity on the tour of South Africa.
"This is reward for the work and leadership skills he showed both on and off the field," Ashton told BBC Radio Five Live.
"He's a rejuvenated player and I thought he played particularly well against what was a very, very strong South Africa front row."
Sale's Mark Cueto is named at full-back, with David Strettle and Jason Robinson on the wings for the Twickenham Test.
At scrum-half, Bristol's Shaun Perry has been given first chance to partner fly-half Jonny Wilkinson, ahead of Andy Gomarsall and Peter Richards.
Ashton admitted that he was still not sure what his strongest starting line-up was, with less than six weeks before their opening World Cup match.
"While I said at the end of the South African tour that it would be great to play our strongest side as soon as possible, in reality we don't know what that is yet," he said.
For all the players involved, the next two weeks are incredibly important
England coach Brian Ashton
"We've got to try out one or two combinations this week and next week."
England, who begin their World Cup defence against USA on 8 September, have two further warm-up games against France, with the sides meeting on 11 August at Twickenham and then a week later in Marseille.
"We're probably looking to put out our strongest XV in the second game against France - for all the players involved, the next two weeks are incredibly important," added Ashton, who also talked up the centre pairing of Hipkiss and Farrell.
"Dan Hipkiss deserves his chance," he said.
"He played really well in the second half of the season and certainly would have gone to South Africa had he not been involved in the Heineken Cup final.
"Andy Farrell has trained exceptionally hard. For the first time since he switched code, he's been able to train like he was before he switched."
The decision to switch Corry to blind-side flanker raised eyebrows after his successful deployment at lock during the Six Nations, but Ashton said he had no qualms about moving the Leicester skipper.
"He may well be in the second row for the World Cup," he said.
"It gives some very good options to have three international-class line-out jumpers in the back row. But don't rule out the possibility of him appearing in the second row a bit further down the line or even on Saturday."
Wasps open-side flanker Tom Rees is continuing his recovery from a knee injury, while Gloucester centre Mike Tindall's hopes are still alive as he regains fitness after his broken leg.
England: Mark Cueto; David Strettle, Dan Hipkiss, Andy Farrell, Jason Robinson; Jonny Wilkinson, Shaun Perry; Andrew Sheridan, Mark Regan, Phil Vickery (captain), Simon Shaw, Steve Borthwick, Martin Corry, Joe Worsley, Nick Easter
Replacements: George Chuter, Matt Stevens, Lewis Moody, Lawrence Dallaglio, Peter Richards, Toby Flood, Mathew Tait