Northampton's New Zealand-born flanker Teimana Harrison will earn his first England cap against Wales at Twickenham on Sunday.
Harrison, who qualifies for England through his Nottingham-born father, will play at No 6, and he is one of four uncapped players in Eddie Jones' 23 for the international, along with Sale Sharks hooker Tommy Taylor, Leicester loosehead prop Ellis Genge and Bath centre Ollie Devoto.
Harrison - who came to England five years ago - takes the place of Chris Robshaw, who is given a rest ahead of the summer tour of Australia, and Jones was unable to consider any Saracens or Exeter players as they are involved in the Aviva Premiership final on Saturday.
Jack Clifford of Harlequins starts at No 8, and James Haskell keeps his place on the openside flank, with Joe Launchbury and Courtney Lawes making up the second-row pairing.
Wasps loosehead Matt Mullan takes the place of Joe Marler - who is taking a break over the summer - at loosehead, and he packs down alongside skipper Dylan Hartley and tighthead Dan Cole.
Leicester's Ben Youngs and Bath's George Ford form the half-back partnership, with Luther Burrell and Jonathan Joseph the midfield pairing.
Harlequins' Marland Yarde is named on the left wing, with club team-mate Mike Brown at full-back and Bath's Anthony Watson on the right wing.
"We've picked a side we believe can beat Wales," said England head coach Jones. "It's a good mixture of experienced players and youth.
"Obviously we have a number of players missing from the squad who are taking part in the Premiership Final but this provides us with a great opportunity to expose other players to Test rugby. This will serve to strengthen the squad's depth as we move towards the 2019 World Cup.
"We've prepared well this week and I'm pleased with the progress the squad have made in the time we've had together. There's been plenty of energy and enthusiasm and you can tell the lads have enjoyed being back in camp.
"As always there were some tight calls on selection and that's how we want it. There are some new faces to the squad. Teimana Harrison gets a start at six, which is a great chance for him to make a statement ahead of the tour to Australia. Ellis Genge and Tommy Taylor have all trained well this week and deserve their spots in the 23.
"This is an important Test match and a great opportunity for us to play some positive, physical rugby. We are a young team learning our craft, Wales are an experienced team; it'll be great test for us.
"We can't wait to get back Twickenham to play in front of a massive crowd. England versus Wales is a special occasion and we look forward to giving our loyal fans something to cheer about."
And Jones says Ellis Genge and Tommy Taylor have earned their places on the bench for this weekend's game.
He went on: "Ellis and Taylor have trained well this week and deserve their spots in the 23. And Luther Burrell has done well too. He lost a fair bit of weight and is looking much better now.
"Inside centre is a position where we've lost one player and so he has the opportunity to show what he's got and possibly put one foot on the plane to Australia."
Meanwhile, the coach admitted it was Harrison's form during the second half of the season which caught his eye: "Teimana is very raw and doesn't have a great rugby background. He came over here as a young kid and decided England is his home.
"His form post-Christmas has been absolutely outstanding both his ball-carrying and defence."
England: 15 Mike Brown, 14 Anthony Watson, 13 Jonathan Joseph, 12 Luther Burrell, 11 Marland Yarde, 10 George Ford, 9 Ben Youngs, 1 Matt Mullan, 2 Dylan Hartley, 3 Dan Cole, 4 Joe Launchbury, 5 Courtney Lawes, 6 Teimana Harrison, 7 James Haskell, 8 Jack Clifford
Replacements: 16 Tommy Taylor, 17 Ellis Genge, 18 Paul Hill, 19 Dave Attwood, 20 Matt Kvesic, 21 Danny Care, 22 Ollie Devoto, 23 Elliot Daly