Louis Rees-Zammit will make his first Six Nations appearance in three years when Wales kick off against England.
The Penarth-born star switches for full-back in Saturday's opener at Twickenham, after scoring two tries in the Autumn internationals against Japan and New Zealand.
He returned to rugby last summer after abandoning his efforts to launch an NFL career.
Although he resumed his career on the wing at Bristol Bears, Rees-Zammit will make his fourth Welsh appearance at full-back, having switched his preferred position.
Elsewhere, Mason Grady is on the replacements bench and in line to make his first Wales appearance since fracturing his ankle during their defeat to Fiji in November 2024.
Scarlets flanker Josh Macleod returns from injury to make his tournament debut, in place of injured skipper Jac Morgan, with Alex Mann and Aaron Wainwright completing the back row.
Ben Thomas returns in the midfield, alongside Scarlets centre Eddie James, with Grady providing cover.
Also on the bench, Harri Carter could make only his second appearance after debuting in their defeat to New Zealand, while Tomos Francis could make his comeback, having last played at the 2023 World Cup.
Head coach Steve Tandy said: "Wales v England is always a special game with all the history behind the fixture. We know they’re playing some outstanding rugby and they’re in great form. But I know how much it means to our players playing for the nation and representing Wales."
"The way the squad trained this week has been great. I want to see us get out and really attack the game on Saturday and give the best account of ourselves. Opening the Six Nations at Twickenham is historic and it’s something we can’t wait to do.”
Wales are looking for their first Six Nations victory since beating Italy in March 2023 as they look to banish the unwelcome memory of back-to-back wooden spoons.
Wales XV to face England: Louis Rees-Zammit (Bristol Bears), Ellis Mee (Scarlets), Eddie James (Scarlets), Ben Thomas (Cardiff Rugby), Josh Adams (Cardiff), Dan Edwards (Ospreys), Tomos Williams (Gloucester), Nicky Smith (Leicester Tigers), Dewi Lake (Ospreys - captain), Archie Griffin (Bath), Dafydd Jenkins (Exeter), Adam Beard (Montpellier), Alex Mann (Cardiff Rugby) Josh Macleod (Scarlets), Aaron Wainwright (Dragons)
Replacements: Liam Belcher (Cardiff), Rhys Carre (Saracens), Tomas Francis (Provence), Ben Carter (Dragons), Taine Plumtree (Scarlets), Harri Deaves (Ospreys), Kieran Hardy (Ospreys), Mason Grady (Cardiff)
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