Taulupe Faletau is named at No. 8 and will make his first appearance for Wales since the 43-19 win against Georgia at Rugby World Cup 2023.
Openside flanker and captain Jac Morgan and blindside flanker James Botham join Faletau in the back row.
Eddie James will make his Guinness Six Nations debut. He starts alongside Nick Tompkins in the Wales midfield.
Hooker Evan Lloyd and tighthead prop Henry Thomas make their second Test starts for Wales with Gareth Thomas again at loosehead.
Will Rowlands and Dafydd Jenkins continue their second-row partnership, scrum-half Tomos Williams and fly-half Ben Thomas are again at half back.
Wings Josh Adams and Tom Rogers and fullback Liam Williams comprise the Wales back three.
Among the Wales replacements Elliot Dee, Nicky Smith, Keiron Assiratti, Freddie Thomas and Aaron Wainwright provide the forward cover.
Rhodri Williams, Dan Edwards and Blair Murray are the replacement backs.
Gatland said: “This has been an important week with a lot of hard work put in during training.
“We want to be accurate and disciplined on Saturday. It’s about our execution and how we manage the game.
“We know Italy are a quality side with physical players and are looking forward to a good contest. We’re excited for the challenge on Saturday.”
Wales team v Italy
15. Liam Williams (Saracens – 93 caps)
14. Tom Rogers (Scarlets – 6 caps)
13. Nick Tompkins (Saracens – 39 capa)
12. Eddie James (Scarlets – 3 caps)
11. Josh Adams (Cardiff Rugby – 60 caps)
10. Ben Thomas (Cardiff Rugby – 8 caps)
9. Tomos Williams (Gloucester Rugby – 60 caps)
1. Gareth Thomas (Ospreys – 36 caps)
2. Evan Lloyd (Cardiff Rugby – 6 caps)
3. Henry Thomas (Scarlets – 5 caps)
4. Will Rowlands (Racing 92 – 37 caps)
5. Dafydd Jenkins (Exeter Chiefs – 20 caps)
6. James Botham (Cardiff Rugby – 17 caps)
7. Jac Morgan (Ospreys – 19 caps) – captain
8. Taulupe Faletau (Cardiff Rugby – 104 caps)
Replacements
16. Elliot Dee (Dragons– 52 caps)
17. Nicky Smith (Leicester Tigers – 50 caps)
18. Keiron Assiratti (Cardiff Rugby – 11 caps)
19. Freddie Thomas (Gloucester Rugby – 2 caps)
20. Aaron Wainwright (Dragons – 53 caps)
21. Rhodri Williams (Dragons – 6 caps)
22. Dan Edwards (Ospreys – 1 cap)
23. Blair Murray (Scarlets – 4 caps)
