Props Samson Lee and Gethin Jenkins suffered injuries in the first half of the victory over Ireland in Cardiff on Saturday and are replaced by Aaron Jarvis and Rob Evans, who will make his first start as head coach Warren Gatland named an otherwise unchanged side.
Lee left the Millennium Stadium on crutches after suffering an Achilles injury while Jenkins strained a hamstring and was replaced at halftime.
Gatland said Lee had suffered a full rupture and his hopes of playing in the World Cup in September were "50-50".
Tighthead prop Lee was due to undergo surgery on Monday but this was postponed because of too much swelling around the injury.
"It is a longer termer that could potentially keep him out of the World Cup," Gatland told reporters on Tuesday.
Wales go into the game in Rome with an outside chance of winning the title. Gatland's side, like England and Ireland, have won three matches but have a significantly inferior points difference to their two main rivals.
"Obviously, it's disappointing for Gethin and Samson, but Rob and Aaron stepped up well last weekend and we expect the same on Saturday," Gatland added.
"The challenge to us is to go to Italy and win, and try and win by a significant margin, but we know that's an extremely tough ask and the first job will be to simply get the result.
"Italy build their confidence around the scrum and line-out drive and that's an area we are going to have to compete strongly in at the start of the match."
Wales made four changes to their bench with Rhys Gill, Ken Owens, Scott Andrews and Gareth Davies coming in.
Wales: 15-Leigh Halfpenny, 14-George North, 13-Jonathan Davies, 12-Jamie Roberts, 11-Liam Williams, 10-Dan Biggar (Ospreys), 9-Rhys Webb; 1-Rob Evans, 2-Scott Baldwin, 3-Aaron Jarvis, 4-Luke Charteris, 5-Alun Wyn Jones, 6-Dan Lydiate, 7-Sam Warburton, 8-Taulupe Faletau
Replacements: 16-Ken Owens, 17-Rhys Gill, 18-Scott Andrews, 19-Jake Ball, 20-Justin Tipuric, 21-Gareth Davies, 22-Rhys Priestland, 23-Scott Williams (Scarlets).
(Writing by Justin Palmer; editing by Ed Osmond)
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