England captain Itoje on bench for Six Nations opener against Wales
Itoje has been grieving the death of his mother Florence, with former skipper Jamie George now leading the side out as they seek to make it 12 wins in a row.
Fellow forward Itoje will, however, take over as captain should he take the field at Twickenham after missing the start of England's preparations to attend his mother's funeral in Nigeria.
Henry Arundell will make his first England start since the 2023 World Cup after being named on the left wing in a team announced unusually early by coach Steve Borthwick on Monday.
Arundell featured in the bronze medal match against Argentina two-and-a-half-years ago but became unavailable when he signed for Paris-based Racing 92 because of a Rugby Football Union rule effectively banning players at non-English clubs from Test duty.
Now at Bath, the 23-year-old flyer made his England comeback as a replacement against Fiji in November.
Arundell's return to the starting side has been aided by the toe injury suffered by Tom Roebuck that has kept him out of action since the defeat of New Zealand in November.
Northampton team-mates Fraser Dingwall and Tommy Freeman form England's midfield as they begin their quest for a first Six Nations title since 2020.
Scrum-half Alex Mitchell lines up alongside veteran fly-half George Ford with full-back Freddie Steward, renowned for his ability under the high ball, and wing Immanuel Feyi-Waboso completing the backline.
Itoje's absence from the starting XV sees Alex Coles and Ollie Chessum pack down in the second row, with Sam Underhill at openside flanker with Henry Pollock and Tom Curry once more primed to make an impact off the bench as members of England's "Bomb Squad".
'Special occasion'
Borthwick has again opted for a split of six forwards and two backs among his eight replacements.
Bevan Rodd and Trevor Davison fill the gaps created by the injury crisis at prop with Will Stuart, Fin Baxter and Asher Opoku-Fordjour missing the entire Six Nations.
Ben Spencer and Marcus Smith are the only backs on the bench with Smith providing full-back as well as fly-half cover.
Wales -- thrashed 68-14 by England in Cardiff last year -- are bidding for their first Six Nations win since 2023, with Borthwick expecting a kicking game from the visitors.
"England versus Wales is always a special occasion in the rugby calendar," he said. "It's a fierce rivalry with a long history and one that brings a huge challenge every time we meet.
"We expect Wales to bring a kicking game, so we'll need to be accurate in how we respond to that challenge."
Wales coach Steve Tandy is due to name his side on Thursday.
England (15-1)
Freddie Steward; Immanuel Feyi-Waboso, Tommy Freeman, Fraser Dingwall, Henry Arundell; George Ford, Alex Mitchell; Ben Earl, Sam Underhill, Guy Pepper; Ollie Chessum, Alex Coles; Joe Heyes, Jamie George (capt), Ellis Genge
Replacements: Luke Cowan-Dickie, Bevan Rodd, Trevor Davison, Maro Itoje, Tom Curry, Henry Pollock, Ben Spencer, Marcus Smith
Coach: Steve Borthwick (ENG)