Tom Wood will captain England in their World Cup warm-up meeting with France while Sam Burgess and Henry Slade are the midfield combination.
The Northampton Saints back-row, who led England in their two-Test tour of Argentina in 2013, will win his 37th cap as Stuart Lancaster's charges start a series of three games leading into the Rugby World Cup.
Wood will pack down alongside Saints team-mate Calum Clark, who makes his Test debut, and Ben Morgan (Gloucester) who returns from injury to play his first international of 2015.
Slade (Exeter Chiefs) and Burgess (Bath) combine in midfield to win maiden England caps from the start while Exeter Chiefs hooker Luke Cowan-Dickie is primed to do so from the bench.
The matchday 23 contains four British and Irish Lions – Alex Corbisiero (Northampton Saints), Owen Farrell (Saracens), Geoff Parling (Exeter Chiefs) and Mako Vunipola (Saracens).
England play France home and away (August 22) in successive weeks followed by the final warm-up international against Ireland at Twickenham on September 5.
"We are really excited to play our first QBE International at Twickenham and to put into practice some what we have been working on for the last six weeks," said Lancaster.
"The lads are itching to get out and play a match and these games give us a chance to look at a wide range of players and combinations before we narrow down our selection further.
"Tom is one of several leaders in the squad and he captained the team well in Argentina when Chris Robshaw was rested, so this is an ideal opportunity to take the armband at Twickenham against what will be a quality French team.
"I'm delighted for the new caps and for Ben Morgan, who has worked so hard to get back to fitness following his injury."
England: 15 Alex Goode, 14 Anthony Watson, 13 Henry Slade, 12 Sam Burgess, 11 Jonny May, 10 Owen Farrell, 9 Richard Wigglesworth, 8 Ben Morgan, 7 Calum Clark, 6 Tom Wood, 5 Geoff Parling, 4 George Kruis, 3 Kieran Brookes, 2 Rob Webber, 1 Mako Vunipola.
Replacements: 16 Luke Cowan-Dickie, 17 Alex Corbisiero, 18 David Wilson, 19 Dave Attwood, 20 James Haskell, 21 Danny Care, 22 Danny Cipriani, 23 Billy Twelvetrees.
Date: Saturday, August 15
Kick-off: 20:00 BST (19:00 GMT)