Ben Te'o returns to the starting line-up against Italy and Sam Simmonds will make his Six Nations debut when England begin the defence of their title in Rome on Sunday.
Te'o has not played since suffering an ankle injury last October, but will make his first England appearance for 11 months after the centre was preferred to Jonathan Joseph.
Simmonds dons the number eight shirt and his Exeter Chiefs team-mate Alec Hepburn could make his debut off the bench at Stadio Olimpico.
Jack Nowell is another Exeter man who was named among the replacements following his recovering from an ankle injury, with Jonny May and Anthony Watson starting on the wings.
England head coach Eddie Jones said: "I have selected the strongest available side to play Italy this weekend and the players are excited to play in Rome.
"Our preparation over the last two weeks has been excellent and the players feel refreshed. We want to start the tournament well and are ready to go hunting against Italy.
"We know we need to get our set piece right, be defensively strong and play with aggression and plenty of energy."
England XV: Mike Brown, Anthony Watson, Ben Te'o, Owen Farrell, Jonny May, George Ford, Ben Youngs, Mako Vunipola, Dylan Hartley (captain), Dan Cole, Joe Launchbury, Maro Itoje, Courtney Lawes, Chris Robshaw, Sam Simmonds.
Replacements: Jamie George, Alec Hepburn, Harry Williams, George Kruis, Sam Underhill, Danny Care, Jonathan Joseph, Jack Nowell.