Itoje, who led the British & Irons Lions to last year's series win over Australia, missed part of England's build-up due to the death of his mother.
Borthwick had been due to name his team on Thursday but went early, doing so on Monday.
Freddie Steward claimed the fullback position, with Marcus Smith again providing cover from the bench. Immanuel Feyi-Waboso and Henry Arundell complete the back three.
It is Arundell's first England start since the 2023 World Cup. He subsequently became unavailable when he signed for French club Racing 92. Considered again for selection after joining Bath he made his Test comeback as a replacement against Fiji in the autumn.
Fraser Dingwall and Tommy Freeman form the centres with Borthwick turning to a familiar combination after the Northampton team-mates were also paired together for last year's emphatic victories over Wales and Australia.
Wales are searching for their first Six Nations victory since 2023 and Borthwick believes their kicking game will be their main weapon at Twickenham.
"England versus Wales is always a special occasion in the rugby calendar. It's a fierce rivalry with a long history and one that brings a huge challenge every time we meet," Borthwick said.
ENGLAND (v Wales, Saturday)
15–Freddie Steward, 14–Immanuel Feyi-Waboso, 13–Tommy Freeman, 12–Fraser Dingwall, 11–Henry Arundell, 10–George Ford, 9–Alex Mitchell, 8–Ben Earl, 7–Sam Underhill, 6–Guy Pepper, 5–Ollie Chessum, 4–Alex Coles, 3–Joe Heyes, 2–Jamie George, 1–Ellis Genge
Replacements: 16–Luke Cowan-Dickie, 17–Bevan Rodd, 18–Trevor Davison, 19–Maro Itoje, 20–Tom Curry, 21–Henry Pollock, 22–Ben Spencer, 23–Marcus Smith
with PA
