Wales began the match on the front foot with a try from Kate Williams before Italy hit back through Sofia Stefan and the boot of Michela Sillari.
A try for Gwenllian Pyrs put Wales ahead at the break, but after the restart, it was all one-way traffic as Francesca Granzotto, Silvia Turani, Vittoria Ostuni Minuzzi and Aura Muzzo confirmed a comfortable victory.
Looking to avoid going winless across an entire Championship for the first time, Wales came out with intent and were rewarded nine minutes in.
A move from a lineout was neatly finished off by Williams to put the visitors ahead in routine fashion.
A warning shot came soon after as Italy came into the game off the back of a penalty against Wales.
After two near-misses, Italy levelled and then moved ahead as Sara Seye and Elisa Giordano combined to set up Stefan.
Sillari kicked a successful conversion to put her side in front for the first time as Wales were left to rue multiple missed tackles.
The outside centre stretched the lead to five with a penalty halfway through the first period before Wales returned to the ascendancy.
However, repeated mistakes meant they were unable to turn their advantage on the pitch to advantage on the scoreboard.
With the clock in the red and Wales camped in Italy’s half, the visitors moved ahead for a second time with the lineout again proving fruitful.
Attempts at going over through Kelsey Jones and Gwen Crab were pushed back by the Italian defence but they were unable to stop Gwenllian Pyrs before Keira Bevan kicked the conversion to see Wales head into the break two points up.
Their lead at the break was Wales’ first-half advantage in the 2025 Championship, but it did not last long.
After the restart, the hosts looked to control play, and it paid off when they hit the front again with three more points off the boot of Sillari.
The rise in tempo from Italy was proving tricky for Wales to handle, and Le Azzure opened up the biggest lead of the game through Francesca Granzotto.
The replacement winger finished off a stunning move from Italy as big carries and fast passes set up Granzotto to dive over before Sillari nailed a difficult conversion.
Italy then kicked into fifth gear as Silvia Turani got Italy’s third, pushing her way through to dot down.
Sean Lynn rang the changes as his team looked to claw their way back into the game, but Italy continued to dominate.
The bonus point was sewn up for Italy in the 64th minute as Vittoria Minuzzi started and finished the move.
The record win over Wales was confirmed with Granzotto’s second try before a last-gasp score from Aura Muzzo saw them score 34 unanswered points to claim a fine victory.