Coach Clive Woodward had claimed no-one runs up cricket scores against Italy anymore, but England looked set to prove him wrong before losing their momentum and letting the visitors off the hook.
Full-back Josh Lewsey, standing in for the injured Jason Robinson, made a sensational start.
He ran in the opening try - his first for England - after just two minutes, turned Italian full-back Mirco Bergamasco inside out on a swerving run for the second, created James Simpson-Daniel's first international touch-down and provided the final pass for centre Mike Tindall's try as England ran riot.
With hooker Steve Thompson forcing his way over for his first England try and Wilkinson defying a swirling win to land four of five conversion attemtps, England led 33-0 with three-quarters of the game still to go.
But Italy stemmed the tide, refused to lie down, and forced England, who took their foot off the accelerator, to defend in the closing stages of the first half.
As England struggled to regain their rhythm, the Italians continued to cause them problems after the interval.
Fly-half Ramiro Pez, who plies his trade for Rotherham in National League Division One, squandered a golden opportunity by dropping the ball on the England line. But 20-year-old Bergamasco finally secured Italy's consolation try in the 59th minute.
England, who used all seven replacements, did respond when Leicester centre Ollie Smith marked his first cap as a second-half substitute by sending Dan Luger racing over in the left-hand corner for England's sixth try in the 69 minute.
Scrum-half Matt Dawson converted in the absence of the Wilkinson and his replacement Charlie Hodgson, who lasted just six minutes before hurting his knee after taking over from the captain.
But after the whirlwind opening, England were far from impressive in the last hour.