George North has been ruled out of Wales' Six Nations opener at home to Scotland on Saturday because of a shoulder injury.
The centre cum wing, whose 118 caps make him by far the most experienced player in the Wales squad, was sidelined after being hurt during the Ospreys' recent European Challenge Cup victory over South African side the Lions.
Owen Watkin and Nick Tompkins will start in midfield instead, with Cardiff full-back Cameron Winnett making a test debut after just 15 games of professional rugby.
Liam Williams' move to Japan had paved the way for the 21-year-old Winnett's start, with wing Louis Rees-Zammit having recently quit rugby union to pursue a career in American football.
Meanwhile, Winnett's Cardiff teammate James Botham – grandson of England cricket great Ian Botham – is recalled for a first Wales appearance since July 2021 in a back row also featuring Tommy Reffell and Aaron Wainwright.
Exeter lock Dafydd Jenkins will captain the side.
At the age of 21, Jenkins is Wales' youngest skipper since a 20-year-old Gareth Edwards, who became one of rugby union's greatest scrum-halves, led the team against Scotland in 1968.
Wales coach Warren Gatland, explaining North's absence, said: "George got quite a big stinger in terms of his shoulder and didn't take part in full training last week, so Owen Watkin comes into the midfield.
Wales have defeated Scotland in 11 successive Cardiff clashes, including nine Six Nations games, since the Scots last triumphed in the Welsh capital in April 2002.
Scotland coach Gregor Townsend is due to name his side later Thursday.
Wales reached the quarterfinals of the Rugby World Cup in France, losing to Argentina, but Scotland failed to get out of a tough pool also featuring eventual champions South Africa and Six Nations title holders Ireland.
Wales (15-1)
Cameron Winnett; Josh Adams, Owen Watkin, Nick Tompkins, Rio Dyer; Sam Costelow, Gareth Davies; Aaron Wainwright, Tommy Reffell, James Botham; Adam Beard, Dafydd Jenkins (capt); Leon Brown, Ryan Elias, Corey Domachowski
Replacements: Elliot Dee, Kemsley Mathias, Keiron Assiratti, Teddy Williams, Alex Mann, Tomos Williams, Ioan Lloyd, Mason Grady
Coach: Warren Gatland (NZL)