Ospreys lock Alun-Wyn Jones will captain Wales for the first time in next week's RBS 6 Nations clash against Italy.
Jones leads a team showing 10 changes and one positional switch from the side beaten 21-16 by France in Paris last Friday night.
The only players retained are Jones, full-back Lee Byrne, wing Shane Williams and number eight Andy Powell, while Jamie Roberts moves from inside to outside centre.
Regular skipper Ryan Jones is on the bench, along with fellow Grand Slam stars from last season in Stephen Jones, Mike Phillips and Gethin Jenkins.
And players rested completely from the Rome-bound matchday 22 on Saturday week include prop Adam Jones, lock Ian Gough and flanker Martyn Williams.
Ospreys centre Gavin Henson is among a raft of players promoted to the starting line-up.
Henson, set to make a first Test match start since last season's Grand Slam-clinching victory over France, replaces Tom Shanklin, with Roberts switching midfield roles.
It is Wales head coach Warren Gatland's third attempt this season to pair Henson and Roberts.
Gatland's hopes were dashed against South Africa during the autumn, and then for Wales' opening Six Nations clash with Scotland because Henson pulled out injured both times.
Other changes following the France loss see starts for wing Mark Jones, fly-half James Hook, scrum-half Dwayne Peel, hooker Huw Bennett, props John Yapp and Rhys Thomas, lock Luke Charteris, plus flankers Jonathan Thomas and Dafydd Jones.
Sale Sharks number nine Peel has not started in Wales' last 12 Tests, playing a support role to Phillips and Gareth Cooper since the Italy Six Nations game more than a year ago.
Peel, who could be in Guinness Premiership action for Sale against Newcastle on Sunday, was originally left out of Gatland's current Six Nations squad, but recalled when Cooper required knee surgery.
Hook, meanwhile, replaces Stephen Jones, with Peel taking over from Phillips and Bennett preferred to Matthew Rees. Newport Gwent Dragons forwards Rhys Thomas and Charteris replace Adam Jones and Gough, respectively.
Wales' dream of achieving back-to-back Grand Slams might be over, but they remain firmly in contention for a successful Six Nations title defence.
They need to beat Italy - and by a sizeable margin - to keep the heat on tournament leaders Ireland, who face Wales in Cardiff later this month.
Wales team to play Italy in the RBS 6 Nations Championship in Rome on Saturday, March 14:
L Byrne (Ospreys); M Jones (Scarlets), J Roberts (Cardiff Blues), G Henson (Ospreys), S Williams (Ospreys); J Hook (Ospreys), D Peel (Sale Sharks); J Yapp (Cardiff Blues), H Bennett (Ospreys), R Thomas (Newport Gwent Dragons), L Charteris (Newport Gwent Dragons), A-W Jones (Ospreys, capt), J Thomas (Ospreys), D Jones (Scarlets), A Powell (Cardiff Blues).
Replacements: M Rees (Scarlets), G Jenkins (Cardiff Blues), B Davies (Cardiff Blues), R Jones (Ospreys), M Phillips (Ospreys), S Jones (Scarlets), T Shanklin (Cardiff Blues).
England's preparations for the Autumn International series were potentially dealt a further blow as Maro Itoje was forced to undergo an x-ray after Saracens' European victory over Scarlets on Saturday night.