The Newcastle fly-half retains his place, despite producing a poor performance when England slumped 26-19 at home to Wales in their tournament opener.
But giant prop Andrew Sheridan has become England's latest injury casualty.
Sheridan, destroyer of the Australian front row during last October's World Cup quarter-final, is replaced by Wasps forward Tim Payne, who wins his sixth cap.
Details of Sheridan's injury will be released at the England training camp in Bath on Wednesday.
It is another huge setback for England, especially given the tough battle they can expect from an Italian front row that includes revered Leicester prop Martin Castrogiovanni.
Sheridan joins centre Mike Tindall (bruised liver), wing David Strettle (foot) and flanker Lewis Moody (Achilles), who were all hurt against Wales, together with Moody's replacement, Wasps' Tom Rees (knee ligament).
England head coach Brian Ashton makes five changes following that crushing Twickenham setback - four of them enforced through injuries.
Newcastle centre Jamie Noon takes over from Tindall in an all-Falcons midfield alongside Wilkinson and Toby Flood. It will be Noon's first England appearance since a knee injury forced him out of the World Cup last September.
Rugby league recruit Lesley Vainikolo, who went on for Strettle last Saturday, retains his place to gain a first Test start, while back-row switches see Bath flanker Michael Lipman and Harlequins number eight Nick Easter both included.
Lipman, London-born but educated in Australia, wins a fourth cap - he has not previously played in the RBS 6 Nations - with World Cup regular Easter returning following a knee injury that has sidelined him since December 29.
Wilkinson kicked 14 points against Wales, leaving him just four short of reaching 1,000 for England.
But his overall display left a lot to be desired. So much so, that some pundits believed Ashton should have dropped him for the first time in an illustrious 10-year Test career.
Ashton had fly-half alternatives in his squad - Danny Cipriani, Charlie Hodgson and Shane Geraghty - yet Wilkinson keeps the number 10 shirt and wins a 67th cap as England's most experienced player in Rome.
Easter's availability means no place in the starting line-up for Gloucester forward Luke Narraway, who started against Wales but now drops down to bench duty.