Webb will partner number 10 Owen Williams, while rookie centres Mason Grady and Joe Hawkins continue their partnership, and Rio Dyer is on the wing. The latter four have only 15 test caps between them.
Josh Adams is on the other wing, while Liam Williams returns in the fullback berth and Louis Rees-Zammit is among the replacements.
With Biggar unavailable, there is no obvious flyhalf cover on the bench, with Hawkins to fill that role if needed.
Italy beat Wales in their previous meeting in Cardiff at the end of the 2022 Six Nations. Neither side have managed a win yet in this year's competition.
"We’re trying to get a handle on where we are and what we have to do," Gatland told reporters. "For a number of players, this could be their last year in a Wales jersey so there has to be that transition going forward.
"We’re not quite where we want to be, but it’s about giving clear messages about the improvements we want to make.
"We’ve done some good review stuff on Italy this week and where their strengths lie. In attack, we’ve probably been a bit lateral. There’s definitely work-ons."
Hooker and captain Ken Owens will have props Wyn Jones and Tomas Francis either side of him, while the second row is made up of Dafydd Jenkins and Adam Beard.
Taulupe Faletau packs down at number eight along with flankers Jac Morgan and Justin Tipuric.
"The message to the players has been that we have to be smart in terms of the way we play but we’ve also got to be brave and make sure that when the opportunities are on we shift the ball," Gatland said.
Wales team:
15. Liam Williams, 14. Josh Adams, 13. Mason Grady, 12. Joe Hawkins, 11. Rio Dyer, 10. Owen Williams, 9. Rhys Webb; 8. Taulupe Faletau, 7. Justin Tipuric, 6. Jac Morgan, 5. Dafydd Jenkins, 4. Adam Beard, 3. Tomas Francis, 2. Ken Owens, 1. Wyn Jones
Replacements: 16. Scott Baldwin, 17. Gareth Thomas, 18. Dillon Lewis, 19. Rhys Davies, 20. Tommy Reffell, 21. Tomos Williams, 22. George North, 23. Louis Rees-Zammit
Allan to start at fullback for Italy
Tommaso Allan will play at fullback for Italy in the clash in Rome on Saturday, taking over from the injured Ange Capuozzo, whose loss for the remainder of the competition is a bitter blow for coach Kieran Crowley.
It is the only change from the side that won praise in their 34-20 loss to Ireland last time out, and the first time regular flyhalf Allan starts at fullback for the Italians.
He will form a back three along with wings Edoardo Padovani and Pierre Bruno, while the impressive midfield duo Juan Ignacio Brex and Tommaso Menoncello maintain their partnership.
Fit-again Paolo Garbisi keeps his place at flyhalf and will partner number nine Stephen Varney.
The front row of the scrum contains props Danilo Fischetti and Simone Ferrari either side of hooker Giacomo Nicotera, while Niccolo Cannone and Federico Ruzza make up the second row. Flankers Sebastian Negri and captain Michele Lamaro pack down with number eight Lorenzo Cannone.
"We’ve recovered well since the last game and this week we’ve been working on the areas where we needed to improve," Crowley said in a media release from Italian Rugby.
"We know the challenge ahead against Wales and look forward to playing and hope to being able to continue to develop the way we want to play."
Italy team:
15. Tommaso Allan, 14. Edoardo Padovani, 13. Juan Ignacio Brex, 12. Tommaso Menoncello, 11. Pierre Bruno 10. Paolo Garbisi, 9. Stephen Varney; 8. Lorenzo Cannone, 7. Michele Lamaro, 6. Sebastian Negri, 5. Federico Ruzza, 4. Niccolo Cannone, 3. Simone Ferrari, 2. Giacomo Nicotera, 1. Danilo Fischetti
Replacements: 16. Luca Bigi, 17. Federico Zani, 18. Marco Riccioni, 19. Edoardo Iachizzi, 20. Giovanni Pettinelli, 21. Manuel Zuliani, 22. Alessandro Fusco, 23. Luca Morisi
