George Ford and Owen Farrell will start together for the first time in over a year when they line up for England against Ireland on Saturday.
Captain Farrell partners Manu Tuilagi in the centres for the first time in a Test match.
Flankers Sam Underhill and Tom Curry are both named in the back row.
“This weekend we will be looking to gain more match fitness and test different sorts of game strategies,” said boss Eddie Jones.
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Ford and Farrell formed a successful partnership for the first two years of Jones’ tenure, before Farrell switched to fly-half regularly last year.
The last time they started in the same midfield was the second Test against South Africa in Bloemfontein last June, which England lost 23-12.
However, with Henry Slade injured and Ben Te’o not selected, Jones has reverted to the two-playmaker combination after England’s defeat by Wales last weekend.
Elsewhere in the backline Jonny May will make his first appearance of the season on the left wing with Joe Cokanasiga switching to the right wing.
Elliot Daly continues at full-back, with Ben Youngs partnering club-mate Ford in the half-backs.
Up front, Joe Marler makes a first start since coming out of international retirement, with Jamie George and Kyle Sinckler also returning.
Mako Vunipola is named on the bench after a long injury lay-off, with brother Billy making his third straight start of the campaign at number eight.
“The players have come back in a very good physical and mental state and we have had a good preparation this week,” added Jones.
“We purposefully made the week short looking ahead to the World Cup where this might happen beyond our control.
“It is the third of four games for us and come 8 September, when we get on the plane, we want to be ready to go. This is another step forward for us.”
England: Daly; Cokanasiga, Tuilagi, Farrell, May; Ford, Youngs; Marler, George, Sinckler, Itoje, Kruis, Curry, Underhill, B Vunipola.
Replacements: Cowan-Dickie, M Vunipola, Cole, Lawes, Wilson, Heinz, Francis, Joseph.
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