Exeter's Jonny Hill will make his England debut against Italy on Saturday after coach Eddie Jones named him as lock partner to Maro Itoje for the game in Rome where the Six Nations title is at stake.
Scrum-half Ben Youngs will win his 100th cap, inside captain and flyhalf Owen Farrell. In the absence of the injured Manu Tuilagi, Jones has opted for the creative centre pairing of Henry Slade and Jonathan Joseph, with George Furbank at fullback.
After much speculation about his back-row options, Jones has returned to the trio who performed so well in the World Cup, with Sam Underhill and Tom Curry flanking Billy Vunipola, making his first appearance since the final defeat by South Africa a year ago this week.
Hooker Jamie George will win his 50th cap.
There are three uncapped players on the bench -- hooker Tom Dunn, centre Ollie Lawrence and winger Ollie Thorley -- while Dan Robson is the backup scrum-half.
The return of fullback Matteo Minozzi is the only change to Italy's starting lineup.
Minozzi missed last Saturday's 50-17 defeat in Ireland because he was playing for Wasps in the English Premiership final against Exeter Chiefs.
Smith kept faith with 20-year-old fly-half Paolo Garbisi, who scored 12 points on his debut last week, including a try.
"In Ireland we showed flashes of our potential and positive signs, but we are aware that we have a lot of work ahead of us," Smith said at a news conference.
"We are a young team that wants to progress and continue to build an identity."
England will hope to beat Italy with a bonus point and then rack up enough points to take the title on points difference, if Ireland do not buck the odds by beating France in Paris with a bonus point in the final game of the championship on Saturday.
Ireland have 14 points to the 13 of England and France. Ireland's points difference is +38, with England on +15 and France on +13. To finish top England would need to secure their bonus point, make up the 23-point deficit on Ireland, and then better any further points difference Ireland might make up with a non-bonus point win.
Italy, already condemned to bottom place again, have lost their last 26 Six Nations matches, stretching back five years, and meet an England side who will be seeking a bonus point haul to put themselves in line to take this year's title.
George Furbank, Anthony Watson, Jonathan Joseph, Henry Slade, Jonny May, Owen Farrell, Ben Youngs, Mako Vunipola, Jamie George, Kyle Sinckler, Maro Itoje, Jonny Hill, Tom Curry, Sam Underhill, Billy Vunipola
Tom Dunn, Ellis Genge, Will Stuart, Charlie Ewels, Ben Earl, Dan Robson, Ollie Lawrence, Ollie Thorley
Matteo Minozzi, Edoardo Padovani, Luca Morisi, Carlo Canna, Mattia Bellini, Paolo Garbisi, Marcello Violi, Jake Polledri, Braam Steyn, Sebastian Negri, Niccolo Cannone, Marco Lazzaroni, Giosue Zilocchi, Luca Bigi, Danilo Fischetti
Gianmarco Lucchesi, Simone Ferrari, Pietro Ceccarelli, David Sisi, Johan Meyer, Maxime Mbanda, Guglielmo Palazzani, Federico Mori.