Flyhalf Danny Cipriani and back rowers Nick Easter and Tom Croft will take their places on an unfamiliar bench as Stuart Lancaster has been forced to deal with a host of injuries for Friday's Six Nations opener against Wales in Cardiff.
Cipriani, who will cover starting flyhalf George Ford, last played a Six Nations game in 2008 while 36-year-old Easter's last England game was the 2011 World Cup quarter-final defeat by France.
Croft was drafted into the squad only last week as injury cover, having missed almost all of last season with a knee injury.
In the team named on Wednesday, Jonathan Joseph and Leroy Burrell will be the starting centres in an inexperienced backline who will be severely tested by the formidable Welsh backs in what should be a red-hot Friday night opening to the championship.
Dan Cole is rushed back for his first start in a year having not played any rugby since December, James Haskell replaces Tom Wood at blindside flanker while George Kruis gets another chance to impress in the second row alongside Dave Attwood.
England: 15-Mike Brown, 14-Anthony Watson, 13-Jonathan Joseph, 12-Luther Burrell, 11-Jonny May, 10-George Ford, 9-Ben Youngs; 8-Billy Vunipola, 7-Chris Robshaw (captain), 6-James Haskell, 5-George Kruis, 4-Dave Attwood, 3-Dan Cole, 2-Dylan Hartley, 1-Joe Marler
Replacements: 16-Tom Youngs, 17-Mako Vunipola, 18-Kieran Brookes, 19-Tom Croft, 20-Nick Easter, 21-Richard Wigglesworth, 22-Danny Cipriani, 23-Billy Twelvetrees.
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