Ben Te'o will start a Test for the first time after being named at outside centre for England's RBS 6 Nations clash with Italy at Twickenham on Sunday.
Te'o replaces Jonathan Joseph, who has been omitted from the matchday 23, to form a new-look centre partnership with Owen Farrell after winning all five of his previous caps off the bench.
Worcester's hard-running rugby league convert made telling contributions during late cameos against France and Wales and head coach Eddie Jones wants to see what impact he might have as a starter.
"Ben Te'o at 13 gives us another way of playing the game and we are excited about seeing him, George Ford and Owen Farrell play together in the midfield," Jones said.
George Ford continues to pull the strings at fly-half but he starts alongside a new half-back partner in Danny Care, who has swapped places with Ben Youngs.
The two remaining changes to the team that toppled Wales 21-16 in Cardiff see Jonny May restored to the right wing, forcing Jack Nowell on to the bench, and James Haskell return at openside.
It will be Haskell's first start since last summer's triumphant tour to Australia after a seven-month absence because of foot surgery.
Haskell was also a significant contributor to the late wins against France and Wales, making strong carries, and the powerful Wasps veteran is rewarded with his return to the back row in place of Jack Clifford.
Henry Slade makes an appearance on the bench where he offers midfield cover, but there is no place among the 23 for Anthony Watson despite his recovery from a hamstring injury.
"Ben Youngs has been outstanding for us at number nine, but Danny Care gets the starting jersey this week," Jones said.
"For the first half he'll give us a lot of speed and running at the base of the ruck as well as the scrum. Ben will then come on and finish the game.
"Tom Wood has been great for us at seven and Jack Clifford did well against Wales but James Haskell has the starting role on Sunday.
"James has come back to a much better level of fitness and we are sure his explosive actions will help us in the first part of the game."
England are targeting a 17th successive Test victory, a total that would leave them one short of the world record 18 wins established by New Zealand.
Italy have been poor so far in this Six Nations, conceding 96 points in the opening two rounds alone, and Jones last week ordered his players to "take them to the cleaners".
World player of the year nominee Farrell will lead the team out at Twickenham in recognition of his 50th cap.
"It is an important Test match for us and our only consideration is to play well," Jones said.
"Italy have a proud record in Test rugby, they beat South Africa in November, and we will not underestimate them.
"I know the Twickenham crowd will give Owen Farrell a big cheer. To reach 50 caps at such a young age is a fine achievement.
"The one thing I know about Owen is that his next 50 are going to be more impressive than his first."
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