Fly-half Diego Dominguez scored 15 points and the Azzurri grabbed three tries to register a 30-22 win - their first in the tournament since the famous debut triumph over Scotland three years ago.
Wales' defence was pierced after just three minutes as Italy made their expected frenzied start.
Prop Giampiero De Carli was the hero as he turned and rolled his way over to end a spell of early Italian pressure.
Wales quickly responded with Northampton's Steve Williams justifying his recall by claiming his second try in 25 games in the seventh minute.
Moments later Italy were punished for two inept challenges deep in Welsh territory as Saracens centre Tom Shanklin raced clear from 60 metres out to grab his third try for his country.
But with Wales claiming that Italian skipper Alessandro Troncon was blocking their defenders, hooker Carlo Festuccia drove over from a few metres out to again level the scores.
Iestyn Harris and Dominguez traded penalties before Italy's Argentina-born prolific points scorer scooped over a drop goal to give his side a three-point lead at half-time.
And as the second half wore on Italy were more in command and it was no surprise when they grabbed a third try after Troncon had pinched the ball from a Welsh scrum. Flanker Andrea De Rossi freed New Zealand-born number eight Matthew Phillips and he drove over the whitewash.
Dominguez converted and added a second drop goal and though Dwayne Peel did grab a try right on full-time with Italy reduced to 14 men after lock Cristian Bezzi had been sin-binned, there was no miraculous comeback for Wales.