Both players are named on the replacements bench for the clash as coach Stuart Lancaster makes five changes to the team which beat France a fortnight ago.
Hartley’s place in the starting line-up goes to Tom Youngs, while Lawes is replaced by James Haskell.
Franklin’s Gardens favourite Tom Wood retains his place and is the only Northampton representative in team, while Wood’s former Saints team-mate Chris Ashton is named on the wing.
Elsewhere, Saracens prop Mako Vunipola will make his first England start.
Vunipola, who won his first seven Test caps as a high-impact replacement, replaces Joe Marler at loosehead and England go into the game with a new half-back combination.
Toby Flood takes over at fly-half from Owen Farrell, who is recovering from a strained thigh muscle suffered against France, and Danny Care gets his chance at scrum-half in place of Ben Youngs.
With Farrell not being risked, Gloucester fly-half Freddie Burns is on the bench and eyeing a second cap, having made a successful debut off the bench in December’s win against New Zealand.
Joining Burns among the replacements is Tom Croft, the Leicester flanker, who returns to the England fold 11 months after a broken neck almost left him paralysed.
Croft made his comeback for Leicester on January 4 and he rejoined the England squad after being given medical clearance to play every week.
After three consecutive victories, Lancaster always intended to “freshen up” the side as England target a victory over Italy that will tee up a shot at the Grand Slam.
Lancaster said: “We were very happy with the way we finished the France game. The impact the replacements made shows that we have competition for places across the board and we have had to make some tight calls.
“Italy will be highly motivated for this game and we will have to perform for the full 80 minutes. I am sure those starting will seize their chance and the bench will also have a significant part to play as the game goes on.
“The support at Twickenham for the Scotland and France games was superb and I am sure the atmosphere will be fantastic again for our final home match of the championship.”
Lancaster had floated the idea of moving Manu Tuilagi to the wing and giving Billy Twelvetrees another start at inside centre but he has decided to keep faith with Chris Ashton.
The Saracens wing scored four of England’s eight tries in this corresponding fixture two years ago and a repeat of that day would tighten England’s grip on the Six Nations title.
England’s points difference is currently 17 better than nearest rivals Wales, who they face in the final round of the championship in Cardiff next Saturday.
England team to play Italy in the RBS 6 Nations at Twickenham on Sunday, March 10 (kick-off 3pm): A Goode (Saracens); C Ashton (Saracens), M Tuilagi (Leicester), B Barritt (Saracens), M Brown (Harlequins); T Flood (Leicester), D Care (Harlequins); M Vunipola (Saracens), T Youngs (Leicester), D Cole (Leicester), J Launchbury (Wasps), G Parling (Leicester), J Haskell (Wasps), C Robshaw (Harlequins, capt), T Wood (Northampton).
Replacements: D Hartley (Northampton), D Wilson (Bath), J Marler (Harlequins), C Lawes (Northampton), T Croft (Leicester), B Youngs (Leicester), F Burns (Gloucester), B Twelvetrees (Gloucester).