George Ford will make his full England debut against Samoa at Twickenham on Saturday - one of six changes made by coach Stuart Lancaster.
Ford starts at fly-half with Owen Farrell moving to inside centre and Ben Youngs replacing Danny Care at scrum-half.
Kyle Eastmond has dropped out of the 23-man squad after sustaining a concussion in the defeat against South Africa last weekend and Farrell moves to the midfield to replace him.
At hooker, Rob Webber starts in place of Dylan Hartley while there are two changes in the back row with James Haskell in for Tom Wood at blind-side flanker and Ben Morgan taking Billy Vunipola's place at No 8.
Wood drops to the bench along with Hartley, with centre Billy Twelvetrees and scrum-half Richard Wigglesworth also earning places among the replacements.
Motivated
"There’s some exciting combinations we want to look at," said England head coach Stuart Lancaster, who is hoping to see his side win for the first time in November after defeats against New Zealand and the Springboks.
"Ben Morgan deserved to get his chance after what he’s one off the bench and Ben Youngs also in great form - and we’re excited to see George Ford get that first start at 10.
"I felt the team that played against New Zealand deserved a second chance and while some player improved there were one or two areas which weren’t as good as I hoped so we get a chance now to look at some other players and combinations."
Farrell's form has come under particular scrutiny, with England's backline looking stilted and lacking in penetration but Lancaster stood by the 23-year-old.
"Owen wasn’t to blame for the performances against New Zealand or South Africa," said Lancaster, who started Farrell at inside center alongside Charlie Hodgson in his first Test in charge of England back in 2012.
"He's a great communicator and leader, and a great support for George - it’s a big step for George to come in to this environment and this team but he is a confident player and he’s ready to take the lead role.
"It’s not true that Owen is undroppable. He has been dropped in the past and this is a combination we wanted to look at."
Team: 15 Mike Brown, 14 Anthony Watson, 13 Brad Barritt, 12 Owen Farrell, 11 Jonny May, 10 George Ford, 9Ben Youngs; 1 Joe Marler, 2 Rob Webber, 3 David Wilson, 4 Dave Attwood, 5 Courtney Lawes, 6 James Haskell, 7 Chris Robshaw (capt), 8 Ben Morgan.
Replacements: 16 Dylan Hartley, 17 Matt Mullan, 18 Kieran Brookes, 19 George Kruis, 20 Tom Wood, 21 Richard Wigglesworth, 22 Billy Twelvetrees, 23 Marland Yarde.
Watch England take on Samoa this Saturday, live on Sky Sports 2 from 6.30pm