Ospreys lock Alun-Wyn Jones will captain Wales in their RBS 6 Nations opener against Italy on Saturday.
Jones takes over from Sam Warburton, who will begin his comeback after two months out with a shoulder injury on the replacements' bench.
Elsewhere, Rhys Priestland has edged out Dan Biggar for fly-half duties, Jamie Roberts returns in midfield after missing this season's autumn Tests, Paul James replaces injured prop Gethin Jenkins and Luke Charteris fills the second-row vacancy left by suspended Ospreys forward Ian Evans.
It had been widely expected that Wales coach Warren Gatland would look to ease Warburton back, rather than start him against Italy.
The Cardiff Blues flanker has not played since Wales' autumn series finale against Australia on November 30.
And in Jones, who skippered the British and Irish Lions to a Test series-clinching victory over the Wallabies in Sydney last summer, Wales have a highly-capable deputy.
Leadership duties might have fallen to Jenkins - Wales captain in the record 30-3 win against England last season - but he is sidelined due to a knee problem, so James starts and Ryan Bevington and Rhodri Jones provide bench cover.
Although Scarlets playmaker Priestland returns at fly-half, there is no place in the match-day 23 for Biggar, with James Hook, Rhys Webb and Liam Williams named as back division replacements.
Charteris' return, meanwhile, comes as Evans reflects on a 12-week ban imposed following his sending-off for stamping during the Ospreys' Heineken Cup defeat against Leinster earlier this month.
Evans will miss the entire Six Nations campaign as he is not eligible to play again until April 21.
With Warburton on bench duty, Justin Tipuric starts at openside flanker and Racing Metro forward Dan Lydiate fills blindside duties alongside number eight Toby Faletau.
And much will be expected of Wales' midfield partnership as fit-again Roberts teams up with in-form Scott Williams as the defending champions go into Six Nations battle minus injured Scarlets centre Jonathan Davies.
"We are looking for a good start," said Gatland, whose team are chasing an unprecedented Six Nations title hat-trick this season.
"We started slowly last year and know we need to be ready from the off.
"Italy started last year's tournament with a win over France, so they will be ready on Saturday and we need to start well and build confidence and momentum.
"It's a strong, experienced side, but there was a lot of discussion about the selection, which is a great position to be in as a coach.
"We've almost everyone fit for selection, which is pretty rare.
"Alun-Wyn will lead the side with Sam starting on the bench, and he has come through training well."
It later emerged that Warburton could end up starting the game after Lydiate flew back to Paris on Tuesday morning.
Lydiate's partner is due to have a child, and the former Newport Gwent Dragons forward has returned to be with her.
It is not known at this stage whether or not Lydiate will take part on Saturday.
Wales team: L Halfpenny (Cardiff Blues); A Cuthbert (Cardiff Blues), S Williams (Scarlets), J Roberts (Racing Metro), G North (Northampton); R Priestland (Scarlets), M Phillips (Racing Metro); P James (Bath), R Hibbard (Ospreys), A Jones (Ospreys), L Charteris (Perpignan), A-W Jones (Ospreys, capt), D Lydiate (Racing Metro), J Tipuric (Ospreys), T Faletau (Newport Gwent Dragons).
Replacements: K Owens (Scarlets), R Bevington (Ospreys), R Jones (Scarlets), A Coombs (Newport Gwent Dragons), S Warburton (Cardiff Blues), R Webb (Ospreys), J Hook (Perpignan), L Williams (Scarlets).