Voyce went on for Wasps colleague Lewsey midway through the first half, and he capped an impressive display by scoring England's final try.
With Voyce promoted to starting duty, Gloucester back James Simpson-Daniel is drafted into the 22 on a bench that again includes World Cup winners Lawrence Dallaglio and Matt Dawson.
Sale Sharks try machine Mark Cueto, meanwhile, has recovered from a knock sustained against Wales to retain his place for the Rome trip, with England head coach Andy Robinson predictably retaining a midfield combination of Jamie Noon and Mike Tindall.
Cueto's fellow wing Ben Cohen wins his 50th cap, making him the 21st England player to reach that milestone.
Lewsey's absence from the England side ends an unbroken sequence of 22 successive starts since he missed the World Cup quarter-final victory over Wales in Brisbane more than two years ago.
He is now battling to try to regain full fitness for England's Calcutta Cup mission against Scotland at Murrayfield on February 25, but given his current form, Voyce should prove a capable deputy.
The 25-year-old Cornishman made his England debut against the USA in 2001, but then had to wait three years for his next opportunity, making starts in tour defeats against New Zealand and Australia, before scoring two tries when the world champions smashed Samoa 40-3 in November.
Voyce was last season's top try-scorer in the Premiership, and he can expect plenty of attacking opportunities when England target their seventh successive Six Nations triumph over Italy.
Simpson-Daniel, meanwhile, will hope for another chance after lasting just 40 minutes during the Samoa clash before injury forced him off. He started that game at outside centre.
England's record at Stadio Flaminio is hugely impressive, having reeled off wins to the tune of 50-9, 45-9 and 59-12 on three previous Six Nations visits.
England team to play Italy in the RBS 6 Nations Championship in Rome on Saturday:
T Voyce (Wasps); M Cueto (Sale Sharks), J Noon (Newcastle), M Tindall (Gloucester), B Cohen (Northampton); C Hodgson (Sale Sharks), H Ellis (Leicester); A Sheridan (Sale Sharks), S Thompson (Northampton), M Stevens (Bath), S Borthwick (Bath), D Grewcock (Bath), J Worsley (Wasps), L Moody (Leicester), M Corry (Leicester, capt).
Replacements: L Mears (Bath), J White (Leicester), S Shaw (Wasps), L Dallaglio (Wasps), M Dawson (Wasps), A Goode (Leicester), J Simpson-Daniel (Gloucester).