Henry Slade had been dropped from England's squad for the Rugby World Cup in France, heading the list of high-profile omissions as coach Steve Borthwick named his 33-man selection for the tournament on Monday.
Slade, 30, featured for England at the last two tournaments and has been a regular since making his debut in 2015, but was dropped by former coach Eddie Jones late last year.
He has not done enough to convince Borthwick that his versatility, which has also seen him previously also play fly-half, fullback and wing for England, is enough of an asset.
No. 8 Alex Dombrandt, flanker Tom Pearson, hooker Jamie Blamire, centre Guy Porter and wing Joe Cokanasiga also miss out.
The quintet all started England's dismal 20-9 loss to Wales in Cardiff on Saturday and look to have paid the price for a dire showing.
Mercurial Marcus Smith is one of three fly-halves along with captain Owen Farrell and George Ford.
England will go into the tournament with three specialist centres in Joe Marchant, Ollie Lawrence and Manu Tuilagi, though Elliot Daly and Farrell can provide cover. The latter will wear the No. 12 jersey if Smith or Ford are preferred at fly-half.
Max Malins and Henry Arundell are versatile back three selections who can cover wing and fullback, and have been selected ahead of Cokanasiga and the experienced Jonny May.
Among the forwards, Billy Vunipola is selected despite questions over his fitness after undergoing two knee operations and will be the only specialist eighthman.
Ollie Chessum is included among the list of locks after suffering a fractured ankle in March while flanker Tom Curry is expected back after his recent ankle injury.
Theo Dan, the 22-year-old Saracens hooker who made his test debut on Saturday, is preferred to Blamire as the third hooker, behind Jamie George and Jack Walker.
England will meet Argentina in their opening Pool D fixture in Marseille on Sept. 9. Japan, Samoa and Chile are the other teams in the group.
England squad
Backs:
Henry Arundell (Racing 92), Danny Care (Harlequins), Elliot Daly, Owen Farrell (both Saracens), George Ford (Sale Sharks), Ollie Lawrence (Bath), Max Malins (Bristol Bears), Joe Marchant (Stade Francais), Marcus Smith (Harlequins), Freddie Steward (Leicester Tigers), Manu Tuilagi (Sale Sharks), Jack van Poortvliet (Leicester Tigers), Anthony Watson (unattached), Ben Youngs (Leicester Tigers).
Forwards:
Ollie Chessum, Dan Cole (both Leicester Tigers), Tom Curry (Sale Sharks), Theo Dan, Ben Earl (both Saracens), Ellis Genge (Bristol Bears), Jamie George (Saracens), Maro Itoje (Saracens), Courtney Lawes, Lewis Ludlam (both Northampton Saints), Joe Marler (Harlequins), George Martin (Leicester Tigers), David Ribbans (Toulon), Bevan Rodd (Sale Sharks), Kyle Sinckler (Bristol Bears), Will Stuart (Bath), Billy Vunipola (Saracens), Jack Walker (Harlequins), Jack Willis (Toulouse).