Roy Hodgson has named four uncapped players in his squad for the upcoming games against Norway and Switzerland, including former Saints star Calum Chambers.
Jack Colback, Chambers - who rose through the Saints academy before moving to Arsenal for £16m this summer - Danny Rose and Fabian Delph are included in a new-look 22-man party.
New Saints goalkeeper Fraser Forster is also in the squad.
Tottenham winger Andros Townsend returns to the squad after missing the World Cup through injury and there is also a place for Everton's 20-year-old defender John Stones.
Chambers has caught the eye at Arsenal since his £16m move from Southampton and has earned a call-up despite the concerns of Gunners boss Arsene Wenger.
Danny Rose has been rewarded for his good early-season form with Tottenham and Fabian Delph comes into the squad because of his progress at Aston Villa.
It is Colback's call-up which comes as the biggest surprise.
The Newcastle midfielder has rarely been mentioned as a possible candidate for England duty, but Hodgson's hand has been forced by a series of injuries.
Kyle Walker (pelvis), Ross Barkley (knee), Theo Walcott (knee), Glen Johnson (thigh), Luke Shaw (hamstring), Michael Carrick (ankle), Jon Flanagan (knee), Adam Lallana (knee), Chris Smalling (groin), Kieran Gibbs (hamstring), Jay Rodriguez (knee) and Andy Carroll (ankle) are all missing through injury.
And with Steven Gerrard, Frank Lampard and Ashley Cole having now retired, there is an obvious lack of experience in the squad, which is set to meet on Sunday night.
Roy Hodgson has named Wayne Rooney as the new England captain.
The 28-year-old Manchester United skipper got the nod ahead of the likes of Chelsea's Gary Cahill and Manchester City's Joe Hart to become the successor to Steven Gerrard, who retired from international football after the World Cup.
Rooney, who has worn the England armband on two previous occasions, will lead a new-look England squad featuring four uncapped players into the upcoming matches against Norway and Switzerland.
England squad for the Euro 2016 qualifier against Switzerland and the friendly against Norway is as follows:
Forster (Southampton), Foster (West Brom), Hart (Manchester City); Baines (Everton), Cahill (Chelsea), Chambers (Arsenal), Jagielka (Everton), Jones (Manchester United), Rose (Tottenham), Stones (Everton); Colback (Newcastle), Delph (Aston Villa), Henderson (Liverpool), Milner (Manchester City), Oxlade-Chamberlain (Arsenal), Sterling (Liverpool), Townsend (Tottenham), Wilshere (Arsenal); Lambert (Liverpool), Rooney (Manchester United), Sturridge (Liverpool), Welbeck (Manchester United).