Newcastle's teenage centre Mathew Tait will make his England debut against Wales in the RBS Six Nations opener in Cardiff on Saturday. The 18-year-old will play alongside his Falcons team-mate Jamie Noon.
England coach Andy Robinson said: "I have never been afraid to select young talented players if they are ready."
And scrum-half Matt Dawson wins a recall, despite being left out of the initial squad after a row over clashing TV and training commitments.
Tait becomes the youngest England player since his Newcastle team-mate Jonny Wilkinson was capped as an 18-year-old almost six years ago.
Tait's call-up comes as a result of England's midfeld injury crisis with Mike Tindall, Will Greenwood and Stuart Abbott all out.
Noon starts ahead of Gloucester's Henry Paul, who has not recovered his place following his substitution after 26 minutes in the autumn international against Australia.
Robinson has also awarded Gloucester flanker Andy Hazell his first Six Nations start.
Hazell will feature at openside flanker, with Lewis Moody moving to the blindside role and Wasps' Joe Worsley lining up at number eight.
In another change to the side that lost to Australia in November, Leicester lock Ben Kay replaces Bath second row Steve Borthwick.
Kay is scheduled to play alongside Danny Grewcock but the Bath star's presence hinges on whether he is cited this week for an alleged stamping incident on Wasps' Lawrence Dallaglio on Saturday.
Dawson's recall comes at the expense of Gloucester's Andy Gomarsall, England's first-choice number nine in November.
Gomrasall is not even on the bench, with Leicester's Harry Ellis acting as Dawson's deputy.
"Selecting the scrum-half position was a close call," said Robinson.
"However I have decided to start Matt Dawson who has shown great form for his club and can offer tremendous experience."
Sale's Charlie Hodgson will continue at fly-half with club colleague Jason Robinson remaining as skipper in the absence of Wilkinson.
Robinson was without a number of injured frontline players - Wilkinson, Stuart Abbott, Richard Hill, Martin Corry and Will Greenwood.
Noon and Hazell have been selected despite suffering injury scares during the latest round of Zurich Premiership action.
Dawson (calf strain) and Moody (hamstring), meanwhile, rested injuries at the weekend and did not play for their clubs.
Newcastle director of rugby Rob Andrew welcomed the call-ups for Tait and Noon, who will win his sixth cap.
Andrew said: "I'm extremely proud of both of them, and this is a massive day in the history of the club."
England: J Robinson (Sale Sharks, capt); M Cueto (Sale Sharks), M Tait (Newcastle), J Noon (Newcastle), J Lewsey (Wasps); C Hodgson (Sale Sharks), M Dawson (Wasps); G Rowntree (Leicester), S Thompson (Northampton), J White (Leicester), D Grewcock (Bath), B Kay (Leicester), L Moody (Leicester), A Hazell (Gloucester), J Worsley (Wasps).
Replacements: A Titterrell (Sale Sharks), P Vickery (Gloucester), S Borthwick (Bath), J Forrester (Gloucester), H Ellis (Leicester), O Barkley (Bath), B Cohen (Northampton).