Wasps' Josh Lewsey will make his first England start since the 2001 summer tour of North America, taking over at full-back from Jason Robinson who limped off during the win over Wales 10 days ago.
Elsewhere, Gloucester's James Simpson-Daniel replaces thigh injury victim Ben Cohen, Bath centre Mike Tindall is back for Charlie Hodgson, scrum-half Matt Dawson also returns and lock Danny Grewcock fills injured skipper Martin Johnson's boots.
And an enforced switch in the back-row due to Neil Back's calf injury sees Wasps flanker Joe Worsley packing down alongside Richard Hill and Lawrence Dallaglio.
Uncapped Leicester centre Ollie Smith features on the bench, along with Wasps lock Simon Shaw and Sale Sharks flanker Alex Sanderson, who find themselves back in an England 22.
England team to play Italy in RBS 6 Nations at Twickenham on Sunday:
J Lewsey (Wasps); J Simpson-Daniel (Gloucester), W Greenwood (Harlequins), M Tindall (Bath), D Luger (Harlequins); J Wilkinson (Newcastle, capt), M Dawson (Northampton); G Rowntree (Leicester), S Thompson (Northampton), R Morris (Northampton), D Grewcock (Bath), B Kay (Leicester), J Worsley (Wasps), R Hill (Saracens), L Dallaglio (Wasps).
Replacements: M Regan (Leeds), M Worsley (London Irish), S Shaw (Wasps), A Sanderson (Sale Sharks), K Bracken (Saracens), C Hodgson (Sale Sharks), O Smith (Leicester).