Saracens prop Mako Vunipola will make his first England start against Italy on Sunday as one of five changes made by head coach Stuart Lancaster from the 23-13 victory over France.
Vunipola, who won his first seven Test caps as a high-impact replacement, replaces Joe Marler at loosehead with Tom Youngs taking over at hooker from Dylan Hartley.
Wasps flanker James Haskell returns on the blindside in place of Courtney Lawes 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.
Lancaster wanted to freshen up the selection because he believes unleashing players who have been restricted to bench duty can enhance England's performance, a point which applies particularly to Care.
"They (Care and Ben Youngs) are unbelievably close. They are both high-quality players, in great form and in great condition and pushing each other," Lancaster said.
"Danny Care has waited patiently for his opportunity. In freshening the team up, sometimes when you have a guy who is desperate to play that can help the team."
Vunipola and Tom Youngs both made strong impressions off the bench against France, tightening up an English which creaked at times, and they have been rewarded.
"Mako gets his first start and everyone is delighted with that. He has thoroughly deserved his chance and we are looking forward to seeing how he goes," Lancaster said.
"All the front rowers looked at that (the scrum) and bringing Mako in for his start and Tom in for his scrummaging and ball carrying, it will hopefully address that."
Farrell is still only kicking at 80% after suffering a thigh strain but, in Flood, Lancaster is able to recall the most experienced member of his squad.
Croft came close to suffering a catastrophic injury with Leicester 11 months ago and his return to the England set-up has been a major boost for Lancaster.
The 27-year-old was eased back into action following his return for the Tigers in January but he has been cleared to play regularly - and looks as good as ever to Lancaster.
"The key point was I wanted to be sure he was back up to speed. He was a key figurehead in the Six Nations last year and while the team has evolved the principles have remained same," Lancaster said.
"He runs great lines in attack, he is back up to speed in our defence and it is great to have him back in the side."
Lancaster is planning for the Italy and Wales games as one project but the players are focusing solely on extending their unbeaten record against the Azzurri.
"I don't look at the bookie's odds because they are irrelevant. What is relevant is what mindset you turn up in," Lancaster said.
"I am always looking through the course of any week, asking are we ready, are we too anxious, are we in the right place?
"We are in a good place going into the game. Those players who are not involved are still 100% behind the team. That is the making of a good team."
Although Italy are rank outsiders, Lancaster will not write them off particularly following the return from suspension of captain Sergio Parisse.
"We know the improvement they have made and the quality they have," Lancaster said.
"Parisse coming back is a huge psychological lift and it adds a huge amount in terms of experience.
"All things point towards Italy putting in a strong performance and we have to be ready."
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).