Luther Burrell and Jonathan Joseph will form a new-look midfield partnership as England recall four British & Irish Lions for Friday’s RBS 6 Nations opener against Wales at the Millennium Stadium.
Dan Cole starts at tighthead prop while Leicester Tigers teammates Tom Youngs and Tom Croft, as well as Saracens loosehead Mako Vunipola are included among the replacements.
Cole comes in for David Wilson to win a 46th cap in a pack showing four changes from the one that started the final autumn International against Australia.
Lock George Kruis and blindside flanker James Haskell replace injured Northampton Saints duo Tom Wood and Courtney Lawes with Billy Vunipola taking over at No.8 from Ben Morgan who is recovering from a broken leg.
Burrell and Joseph take up the centre berths in the only changes to the backs and get the nod over Billy Twelvetrees while Kyle Eastmond and Manu Tuilagi are both out injured.
As expected, Nick Easter and Danny Cipriani will make their international return from the bench.
Elsewhere, powerful Newcastle Falcons tighthead Kieran Brookes will look to continue a string of eye-catching cameos stretching back to his Test debut against New Zealand last June.
Richard Wigglesworth and Billy Twelvetrees stave off stiff competition to claim the final two spots, both boasting previous experience of the Cardiff atmosphere and composed game management.
Lancaster said: “We’ve had to make some tight calls but we are excited about the side selected for what will be a big challenge.
“JJ has been one of the form centres in the country. He and Luther have trained well together and this is a big opportunity for both of them.
“Billy Vunipola has also been playing well for Saracens and it’s good to be able to give George Kruis his first international start after his impressive run off the bench in November.
“Dan Cole and James Haskell bring a lot of experience, as do the bench, and their contribution will be crucial on Friday night.”
England: Mike Brown, Anthony Watson, Jonathan Joseph, Luther Burrell, Jonny May, George Ford, Ben Youngs; Joe Marler, Dylan Hartley, Dan Cole, Dave Attwood, George Kruis, James Haskell, Chris Robshaw (captain), Billy Vunipola
Replacements: Tom Youngs, Mako Vunipola, Kieran Brookes, Tom Croft, Nick Easter, Richard Wigglesworth, Danny Cipriani, Billy Twelvetrees.
Video courtesy of Nick Heath @rugbymedia.