Ben Morgan has been recalled to the England squad for the November internationals but there is no place for Danny Cipriani in a 36-man squad which includes eight uncapped players.
Morgan has not played for his country since the 2015 World Cup, but the number eight is set to make his comeback next month amid an injury crisis.
Billy Vunipola and Sam Simmonds are ruled out with a fractured arm and a serious knee injury respectively, while Nathan Hughes is unavailable for the first three Tests after being hit with a six-week ban.
Mako Vunipola, Chris Robshaw, Joe Launchbury, Jonathan Joseph and Anthony Watson were among the other players that Eddie Jones was unable to call upon.
"We can only control what we can control and injuries have happened," Jones said in an RFU statement.
"It gives an opportunity for some good new players to play some important Tests for England while players who have been in the squad before, will have to take on more responsibility.
"I'm really happy with the squad."
Fly-half Cipriani misses out for the matches against South Africa, Japan, New Zealand and Australia despite an impressive start to his Gloucester career.
Dylan Hartley and Owen Farrell have been named as co-captains, while Joe Cokanasiga, Nathan Earle, Ted Hill and Zach Mercer will be hoping to earn their first caps.
Ben Moon, Michael Rhodes, Nick Schonert and Elliott Stooke are the other uncapped players in a squad that will fly out to Portugal for a training camp next week.
England squad:
Forwards: Tom Curry, Charlie Ewels, Jamie George, Dylan Hartley, Alec Hepburn, Ted Hill, Maro Itoje, George Kruis, Courtney Lawes, Zach Mercer, Ben Moon, Ben Morgan, Michael Rhodes, Nick Schonert, Brad Shields, Kyle Sinckler, Elliott Stooke, Sam Underhill, Harry Williams, Mark Wilson.
Backs: Chris Ashton, Mike Brown, Danny Care, Joe Cokanasiga, Elliot Daly, Nathan Earle, Owen Farrell, George Ford, Alex Lozowski, Jonny May, Jack Nowell, Henry Slade, Ben Te'o, Manu Tuilagi, Richard Wigglesworth. Ben Youngs.
