Jack Nowell will start for England for the first time since 2019 on Sunday, with Marcus Smith retaining his place at fly-half for their Six Nations trip to Italy.
Harry Randall is set to earn his third international cap in Rome at scrum-half, while Joe Marchant moves into midfield, one of the two positional changes made by head coach Eddie Jones.
Jamie George replaces Luke Cowan-Dickie at hooker and forms a front-row unit with vice-captain Ellis Genge and Will Stuart.
Charlie Ewels is handed a start at lock as Maro Itoje shifts into the back row. Joe Launchbury, who was brought into camp this week after Lewis Ludlam's injury, does not make the match-day squad.
Off the bench, Ben Youngs could become the joint most-capped England men's player of all time. The 32-year-old will add to his 113 caps if he takes to the field at the Stadio Olimpico.
Ollie Chessum is in line to make his England debut off the bench.
"We've set ourselves the target of playing really well and lighting up Rome," Jones said.
"We've made some changes and this is the best side to face Italy. We want to start fast and take the game to them. It's a great opportunity for some players to start the game as opposed to finishing the game."
Bristol scrum-half Randall was an unused replacement during England's trip to Murrayfield, where they lost narrowly to Scotland, but Jones has been impressed by the 24-year-old's work in training.
"He's very good in broken play, he's got a good solid pass on him and his kicking game is improving," Jones said.
In England's front row, there is no starting role for Cowan-Dickie, who took to social media earlier in the week to apologise to England's supporters after conceding a penalty try at Murrayfield.
When asked if Cowan-Dickie's omission was due to that moment, Jones was emphatic in his response.
"No not at all," the head coach said. "He hasn't been able to train this week, he did a little bit today and we've got two very good hookers there."
In midfield, Marchant has moved in from the wing and joins up with Henry Slade. Prior to the Murrayfield Test, Marchant had to isolate after testing positive for Covid-19 and Jones has backed the 25-year-old to provide the team with a different dynamic this week.
"Joe is a good strong runner," Jones said. "He can hit the front line really well, which we maybe missed a little bit last weekend.
"Given that he had such restricted training before Scotland it was difficult for him to play 13 last week, so Elliot will move back as a finisher."
Taking Marchant's place out wide will be Exeter Chiefs' Nowell, who is making a welcome full return to international rugby after a difficult period plagued with injuries.
"Jack has had three solid weeks of training with us and we feel he's ready to play," added Jones. "He has that work-rate, that bounce in his step. I haven't seen him this sharp since 2016."
In England's rejigged back row, Alex Dombrandt replaces Sam Simmonds at No 8 and Itoje moves in at blindside flanker.
"When we look at the team, we try to maximise our resources. Sam Simmonds played very well at No 8 but we're going to finish with him against Italy," Jones said.
"We want to see Alex Dombrandt play in a game that we think will really suit him. Matches against Italy tend to be more open and unstructured, so we feel that it's a great game for him to start at No 8.
"Tom Curry picks himself at seven and then we've gone for a big six. We want to get a bit more running out of Maro in terms of his attack and this is a great opportunity for him."
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England have never been defeated by Italy in the Six Nations and, although the Azzurri have lost their last 33 fixtures in the competition, Jones is prepared to face a good side on Sunday.
He said: "They're a well-coached team. They've made some really rapid progress under Kieran Crowley, who we know is a very good coach.
"They've got some good young players coming through and if you look at the history of their U20s over the last four or five seasons, they've done exceptionally well.
"Italy are not a team that you can underestimate, you have to play well to beat them and I'm sure Kieran is going to have them well prepared."
Italy's head coach Kieran Crowley has made three amendments from the side that lost 37-10 to France in Paris.
Federico Mori arrives on the wing and replaces Tommaso Menoncello, who became the youngest Six Nations try scorer in 55 years in the opening weekend.
Braam Steyn comes into their back row and Pietro Ceccarelli is given the nod at tighthead prop. Replacement front-row forward Tiziano Pasquali and Sebastian Negri drop to the bench.
England XV: 15. Freddie Steward, 14. Max Malins, 13. Joe Marchant, 12. Henry Slade (vice-captain), 11. Jack Nowell, 10. Marcus Smith, 9. Harry Randall; 1. Ellis Genge (vice-captain), 2. Jamie George, 3. Will Stuart, 4. Charlie Ewels, 5. Nick Isiekwe, 6. Maro Itoje, 7. Tom Curry (captain), 8. Alex Dombrandt.
Replacements: 16. Luke Cowan-Dickie (vice-captain), 17. Joe Marler, 18. Kyle Sinckler, 19. Ollie Chessum, 20. Sam Simmonds, 21. Ben Youngs, 22. George Ford, 23. Elliot Daly.
Italy XV: 15. Edoardo Padovani, 14. Federico Mori, 13. Juan Ignacio Brex, 12. Marco Zanon, 11. Montanna Ione, 10. Paolo Garbisi, 9. Stephen Varney, 1. Danilo Fischetti, 2. Gianmarco Lucchesi, 3. Pietro Ceccarelli, 4. Niccolo Cannone, 5. Federico Ruzza, 6. Braam Steyn, 7. Michele Lamaro (captain), 8. Toa Halafihi.
Replacements: 16. Epalahame Faiva, 17. Cherif Traore, 18. Tiziano Pasquali, 19 David Sisi, 20. Sebastian Negri, 21. Giovanni Pettinelli, 22. Alessandro Fusco, 23. Leonardo Marin.