"It's great to be able to give Mako a chance in the squad," said Lancaster. "He has come through our age grade sides and made a real impact at Saracens.
"Likewise Tom Youngs, who was with us on tour in South Africa, and we know what James Haskell and Ugo Monye are capable of if they get their opportunity."
While Lancaster has had to consider a host of injuries and recent retirements, Tom Wood and Courtney Lawes will return to the set-up after missing out on the South African tour in the summer due to respective injury problems.
England begin their series against Fiji on November 10, which will be followed by battles against Australia, South Africa and New Zealand.
England squad in full:
Forwards: Mouritz Botha (Saracens), Dan Cole (Leicester Tigers), James Haskell (London Wasps), Phil Dowson (Northampton Saints), Dylan Hartley (Northampton Saints), Tom Johnson (Exeter Chiefs), Courtney Lawes. (Northampton Saints), Joe Marler (Harlequins), Ben Morgan (Gloucester Rugby), Tom Palmer (London Wasps), Geoff Parling (Leicester Tigers), Chris Robshaw (Harlequins), Mako Vunipola (Saracens), Thomas Waldrom (Leicester Tigers), David Wilson (Bath Rugby), Tom Wood (Northampton Saints), Tom Youngs (Leicester Tigers)
Backs: Anthony Allen (Leicester Tigers), Chris Ashton (Saracens), Brad Barritt (Saracens), Mike Brown (Harlequins), Danny Care (Harlequins), Lee Dickson (Northampton Saints), Owen Farrell (Saracens), Toby Flood (Leicester Tigers), Alex Goode (Saracens), Jonathan Joseph (London Irish), Ugo Monye (Harlequins), Charlie Sharples (Gloucester Rugby), Manu Tuilagi (Leicester Tigers), Jordan Turner-Hall (Harlequins), Ben Youngs (Leicester Tigers)