George Ford will start his first international for England in Saturday’s QBE International against Samoa at Twickenham.
The Bath Rugby fly half takes over from Saracens’ Owen Farrell and will be partnered by his former Leicester Tigers team-mate Ben Youngs at half back.
Farrell switches to inside centre while James Haskell (Wasps) and Ben Morgan (Gloucester Rugby) replace Tom Wood (Northampton Saints) and Billy Vunipola (Saracens) respectively in the back row. Rob Webber (Bath Rugby) comes in at hooker for Dylan Hartley (Northampton Saints).
England Head Coach Lancaster said: "Those selected have a great opportunity to show what they can do against what will be a highly motivated Samoa team.
"It's great to give George a start in this series, having missed the summer tour through injury. He has been impressive in camp and is now fully up to speed with the game plan and he is ready to run the game. Owen switches to 12 and I am sure will support George well. In the back row both James and Ben have been in great form and I am sure they will bring their physical presence to the game.
"Hooker is another competitive position and we believe Rob is ready for the start and will continue the progress he made on the New Zealand tour."
England (v Samoa, QBE International, Saturday, November 22, 7pm, live on Sky Sports HD)
15 Mike Brown (Harlequins, 31 caps)
14 Anthony Watson (Bath Rugby, 2 caps)
13 Brad Barritt (Saracens, 20 caps)
12 Owen Farrell (Saracens, 27 caps)
11 Jonny May (Gloucester Rugby, 9 caps)
10 George Ford (Bath Rugby, 4 caps)
9 Ben Youngs (Leicester Tigers, 40 caps)
1 Joe Marler (Harlequins, 24 caps)
2 Rob Webber (Bath Rugby, 10 caps)
3 David Wilson (Bath Rugby, 39 caps)
4 Dave Attwood (Bath Rugby, 14 caps)
5 Courtney Lawes (Northampton Saints, 34 caps)
6 James Haskell (Wasps, 51 caps)
7 Chris Robshaw (Harlequins, capt, 30 caps)
8 Ben Morgan (Gloucester Rugby, 25 caps)
16 Dylan Hartley (Northampton Saints,59 caps)
17 Matt Mullan (Wasps, 7 caps)
18 Kieran Brookes (Newcastle Falcons,4 caps)
19 George Kruis (Saracens, 2 caps)
20 Tom Wood (Northampton Saints, 32 caps)
21 Richard Wigglesworth (Saracens, 14 caps)
22 Billy Twelevetrees (Gloucester Rugby, 14 caps)