Lock David Attwood (Bath Rugby), flanker Matt Kvesic (Gloucester Rugby), No.8 Billy Vunipola (Saracens), centre Kyle Eastmond (Bath Rugby) and wings Christian Wade (London Wasps) and Marland Yarde (London Irish) step up into the 33-man group.
All bar Attwood won first caps on England's successful summer tour to Argentina, when the Pumas were beaten 32-3 in Salta and 51-26 in Buenos Aires.
Head Coach Lancaster said: "This was the toughest EPS selection we've had to make with fierce competition for places in every area of the squad after an excellent summer for England players at all levels.
"Twelve current England players were part of a victorious British & Irish Lions tour, eight others won their first caps in Argentina, a number of rested senior players will have benefited from their break and the future looks healthy after our Under 20 side won the Junior World Championship for the first time.
"Christian Wade and Marland Yarde brought their outstanding Aviva Premiership form to the tour, Kyle Eastmond showed the potential he has and by including him in the squad we get a chance to work with him some more as we build towards the QBE Internationals. Up front David Attwood adds a physical presence to the second row and in Matt Kvesic and Billy Vunipola we have young back row players who will challenge our more established back row players hard."
Hooker Dylan Hartley (Northampton Saints) is named in the squad and will return to action in September after an 11-week suspension following his sending off in the Aviva Premiership final.
Lancaster said: "I had a long hard think about it and a long conversation with him. I wanted to be reassured that he understands where the line is, what is right and what is wrong. He accepts that and he knows he needs a strong start to the season with Northampton as changes can be made with Rob Webber and David Paice pushing hard.
"Unfortunately we can only have 33 in the Senior EPS but those who just missed out have plenty to offer. They are still very much in the international picture and there is flexibility built into the system that facilitates that."
There are first England Saxons call-ups for Jack Nowell (Exeter Chiefs), one of the 2013 Junior World Championship winners, and Luke Wallace (Harlequins) and the squad also includes the return of 2007 World Cup finalist Mathew Tait (Leicester Tigers).
Lancaster said: "Jack Nowell played well for his club, he played well for England, he's an exciting young player and the sooner we get him into the squad and start working with him, the better.
"Mathew Tait was in great from at the end of last season and he is a quality player. With the players we've got in the back three he's going to add to that and put pressure on the ones above.
"We've got some young forwards coming through. The likes of Luke Wallace, Will Fraser, Ed Slater and George Kruis are the types of players we want pushing through, then hopefully their form and fitness will push them through into the senior squad.
"The task for all of them and those in the Saxons is to be in peak form and pushing for places in the team for the QBE Internationals against Australia, Argentina and New Zealand in November. We very much see this as a 65-man squad and we regularly see players pushing into the Squad and the team from the Saxons. Form and fitness will be the deciding factor in November."
Both squads will meet at Loughborough later this month for a three-day training camp and the senior squad reconvenes a fortnight before facing Australia on November 2. The Saxons are due to face the O2 Ireland Wolfhounds and Scotland A early in 2014.
ENGLAND SENIOR EPS (33)
David Attwood (Bath Rugby)
Dan Cole (Leicester Tigers)
Alex Corbisiero (Northampton Saints)
Tom Croft (Leicester Tigers)
Dylan Hartley (Northampton Saints)
Matt Kvesic (Gloucester Rugby)
Joe Launchbury (London Wasps)
Courtney Lawes (Northampton Saints)
Joe Marler (Harlequins)
Ben Morgan (Gloucester Rugby)
Geoff Parling (Leicester Tigers)
Chris Robshaw (Harlequins)
Billy Vunipola (Saracens)
Mako Vunipola (Saracens)
David Wilson (Bath Rugby)
Tom Wood (Northampton Saints)
Tom Youngs (Leicester Tigers)
Chris Ashton (Saracens)
Mike Brown (Harlequins)
Freddie Burns (Gloucester Rugby)
Danny Care (Harlequins)
Lee Dickson (Northampton Saints)
Owen Farrell (Saracens)
Toby Flood (Leicester Tigers)
Ben Foden (Northampton Saints)
Alex Goode (Saracens)
Kyle Eastmond (Bath Rugby)
Manusamoa Tuilagi (Leicester Tigers)
Billy Twelvetrees (Gloucester Rugby)
Christian Wade (London Wasps)
Marland Yarde (London Irish)
Ben Youngs (Leicester Tigers)
ENGLAND SAXONS EPS (32)
Calum Clark (Northampton Saints)
Jordan Crane (Leicester Tigers)
Paul Doran Jones (Harlequins)
Will Fraser (Saracens)
James Haskell (London Wasps)
Tom Johnson (Exeter Chiefs)
Graham Kitchener (Leicester Tigers)
George Kruis (Saracens)
Kearnan Myall (London Wasps)
David Paice (London Irish)
George Robson (Harlequins)
Ed Slater (Leicester Tigers)
Henry Thomas (Sale Sharks)
Thomas Waldrom (Leicester Tigers)
Luke Wallace (Harlequins)
Rob Webber (Bath Rugby)
Nick Wood (Gloucester Rugby)
Anthony Allen (Leicester Tigers)
Luther Burrell (Northampton Saints)
Elliot Daly (London Wasps)
George Ford (Bath Rugby)
Jonathan Joseph (Bath Rugby)
Jonny May (Gloucester Rugby)
Ugo Monye (Harlequins)
Stephen Myler (Northampton Saints)
Jack Nowell (Exeter Chiefs)
Charlie Sharples (Gloucester Rugby)
Joe Simpson (London Wasps)
David Strettle (Saracens)
Mathew Tait (Leicester Tigers)
Joel Tomkins (Saracens)
Richard Wigglesworth (Saracens)