Alun-Wyn Jones will start in the second row alongside Luke Charteris, with Toby Faletau, Justin Tipuric and Dan Lydiate rekindling their back row partnership.
Up front, Paul James will win his 49th cap alongside Adam Jones and hooker Richard Hibbard.
In the back division, Rhys Priestland has been preferred at fly half to last season's first choice Dan Biggar, who hasn't even made the substitutes bench.
Jamie Roberts and Scott Williams will join up in midfield while the tried and tested back three of Halfpenny, Cuthbert and North complete Wales' starting fifteen.
– Warren Gatland
We are looking for a good start, 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.
Warburton will be joined on the bench by Scarlets forward pair Ken Owens and Rhodri Jones, as well as Ryan Bevington and Andrew Coombs.
Ospreys scrum half Rhys Webb deputises at half-back, alongside James Hook and Scarlets back Liam Williams.
WALES SQUAD TO PLAY ITALY:
Leigh Halfpenny (Cardiff Blues), Alex Cuthbert (Cardiff Blues), Scott Williams (Scarlets), Jamie Roberts (Racing Metro), George North (Northampton Saints), Rhys Priestland (Scarlets), Mike Phillips (Racing Metro), Paul James (Bath Rugby), Richard Hibbard (Ospreys), Adam Jones (Ospreys), Luke Charteris (Perpignan), Alun-Wyn Jones (CAPT – Ospreys), Dan Lydiate (Racing Metro), Justin Tipuric (Ospreys), Taulupe Faletau (Newport Gwent Dragons).
Replacements: Ken Owens (Scarlets), Ryan Bevington (Ospreys), Rhodri Jones (Scarlets), Andrew Coombs (Newport Gwent Dragons), Sam Warburton (Cardiff Blues), Rhys Webb (Ospreys), James Hook (Perpignan), Liam Williams (Scarlets).