Andrew Coombs is the surprise new cap in the Wales side to face Ireland in Saturday's Six Nations opener at the Millennium Stadium.
The 28-year-old, who has switched from the back row for Newport Gwent Dragons this season, fills Wales' vacancy in the second row and partners Ian Evans.
Dan Biggar starts at fly-half, while tight-head prop Adam Jones returns.
Scarlet Aaron Shingler is at blind-side flanker, with Sam Warburton and Toby Faletau in the back row.
Evans will play his first game since he injured his knee playing for Wales in mid-November, but his fellow Osprey Ryan Jones misses out with a dislocated thumb.
Coombs, who stands at 6ft 4in, has played for Pontypool and Newport in the Premiership and was one of five uncapped players named in the Wales squad.
Locks Alun Wyn Jones, Luke Charteris and Bradley Davies are all out injured and Wales interim head coach Rob Howley has given Evans, who played every minute of last year's Grand Slam, every chance to prove his fitness.
Uncapped Harlequins lock Olly Kohn, 31, is on the bench having
That means no place for Osprey James King or Cardiff Blues' Lou Reed in the match squad.
With Dan Lydiate injured, Wales had hinted at playing both open-side flankers Warburton and Justin Tipuric at six and seven in the back row.
But with the raft of injuries at lock, playing 6ft 5in Scarlets flanker Shingler at blind-side provides another option for Wales at the line-out.
Biggar has held off the challenge of James Hook for a chance to make the number 10 shirt his own, with Rhys Priestland missing due to an Achilles tendon injury.
The Ospreys stand-off has been the form number 10 in regional rugby this season and is preferred to Perpignan play-maker Hook who is named on the bench.
Triple Grand Slam-winner Adam Jones returns at tight-head prop after missing Wales' winless autumn campaign with a knee injury and packs down in an all British and Irish Lions front row alongside Gethin Jenkins and Matthew Rees.
Wing Eli Walker had been tipped to win his first cap after an impressive start to the season but the Osprey has been struggling with a hamstring problem, so George North and Alex Cuthbert continue as Wales' giant wings.
Jamie Roberts and Jon Davies form a solid centre partnership, while Mike Phillips retains the scrum-half jersey.
WALES: Leigh Halfpenny (Blues); Alex Cuthbert (Blues), Jonathan Davies (Scarlets), Jamie Roberts (Blues), George North (Scarlets); Dan Biggar (Ospreys), Mike Phillips (Bayonne); Gethin Jenkins (Toulon), Matthew Rees (Scarlets), Adam Jones (Ospreys), Andrew Coombs (Dragons), Ian Evans (Ospreys), Aaron Shingler (Scarlets), Sam Warburton (Blues, capt), Toby Faletau (Dragons).
REPLACEMENTS: Ken Owens (Scarlets), Paul James (Bath), Craig Mitchell (Exeter), Olly Kohn (Harlequins), Justin Tipuric (Ospreys), Lloyd Williams (Blues), James Hook (Perpignan), Scott Williams (Scarlets).
IRELAND: R Kearney; C Gilroy, B O'Driscoll, G D'Arcy, S Zebo; J Sexton, C Murray; C Healy, R Best, M Ross; M McCarthy, D Ryan; P O'Mahony, S O'Brien, J Heaslip (capt).
REPLACEMENTS: S Cronin, D Kilcoyne, D Fitzpatrick, C Henry, D O'Callaghan, E Reddan, R O'Gara, K Earls.
Forwards: Scott Andrews (Blues), Craig Mitchell (Exeter Chiefs), Adam Jones (Ospreys), Paul James (Bath), Gethin Jenkins (Toulon), Ryan Bevington (Ospreys), Richard Hibbard (Ospreys), Ken Owens (Scarlets), Matthew Rees (Scarlets), Ryan Jones (Ospreys), Lou Reed (Blues), Ian Evans (Ospreys), James King (Ospreys), Andrew Coombs (Dragons), Olly Kohn (Harlequins), Josh Turnbull (Scarlets), Josh Navidi (Blues), Aaron Shingler (Scarlets), Justin Tipuric (Ospreys), Sam Warburton (Blues), Toby Faletau (Dragons), Andries Pretorius (Blues)
Backs: Tavis Knoyle (Scarlets), Mike Phillips (Bayonne), Lloyd Williams (Blues), Dan Biggar (Ospreys), James Hook (Perpignan), Jonathan Davies (Scarlets), Jamie Roberts (Blues), Scott Williams (Scarlets), Alex Cuthbert (Blues), George North (Scarlets), Eli Walker (Ospreys), Leigh Halfpenny (Blues), Liam Williams (Scarlets), Lee Byrne (Clermont).