England head coach Steve Borthwick has dropped Marcus Smith and selected Owen Farrell to start at fly-half against Italy in the Six Nations on Sunday.
Borthwick has moved his captain from inside centre, where he played in the defeat against Scotland.
Ollie Lawrence partners Henry Slade in a totally new centre partnership, with Joe Marchant not in the 23.
Jack Willis replaces Ben Curry in the back row while London Irish wing Henry Arundell is among the replacements.
England: Steward; Malins, Slade, Lawrence, Hassell-Collins; Farrell (c), Van Poortvliet; Genge, George, Sinckler; Itoje, Chessum; Ludlam, Willis, Dombrandt
Replacements: Walker, M Vunipola, Cole, Isiekwe, Earl, Mitchell, M Smith, Arundell
The big decision for Borthwick surrounded who he would choose at fly-half and it is Harlequins' Smith - who has yet to consistently show his club form on the international stage - who has paid the price for last weekend's loss to Scotland.
Exeter's Slade returns from a hip injury to partner the in-form Lawrence, while Marchant - a starter in midfield alongside Farrell last week - is not even a replacement.
The only other change in the starting XV is Willis being named at openside flanker in place of Curry, who like Marchant is left out of the matchday squad altogether.
England are seeking to recover from their opening-round defeat by Scotland and claim the first win of Borthwick's tenure.
Speaking at his news conference on Friday, Borthwick focussed on his selection in the centre rather than his choice at fly-half.
"It is fantastic to welcome Henry Slade back," said England's new head coach.
"He is a player that has played very well for his club, has great attributes in the centre and a fantastic left foot.
"Ollie Lawrence has played really well all season for his club [Bath] and is on form. We have some exciting players there and that is why we have made the change."
Borthwick emphasised the need for patience as he and his coaching staff try to imprint their ideas on the squad - but believes there are positive signs.
The former Leicester coach added: "Notwithstanding the disappointment of last weekend's Calcutta Cup result, we know that in a very short space of time positive steps have been taken towards the manner and style in which we want to play.
"We are at the start of what is a completely new cycle. The implementation of new systems does take time.
"I have selected a team that I believe is best placed to meet the specific challenges that Italy will bring. It is a selection of players whose form, individual strengths and combined qualities suit the way we want to play against Italy."
The Azzurri welcome Edoardo Padovani back into the starting line-up for the first time since his try ended their 36-game losing run with a last-gasp win over Wales on the final day of last year's tournament.
Saracens prop Marco Riccioni will make his first start since November 2021 while exciting full-back Ange Capuozzo is in line to face England for the first time.
Italy: Capuozzo; Padovani, Brex, Morisi, Menoncello; Allan, Varney; Fischetti, Nicotera, Riccioni, N Cannone, Ruzza, Negri, Lamaro, L Cannone
Replacements: Bigi, Zani, Ferrari, Iachizzi, Polledri, Zuliani, Fusco, Bruno