Cipriani has made a strong start to the season at Gloucester and was named Gallagher Premiership player of the month for September, yet is missing from the 36-man group named for Tests against South Africa, New Zealand, Japan and Australia.
The 30-year-old playmaker started England’s most recent game against South Africa in June and set-up the pivotal try for Jonny May but having been watched by Eddie Jones four times this season, he has been left out.
Owen Farrell and George Ford are present as the recognised fly-halves, although Henry Slade and Alex Lozowski provide cover in the position.
For the first time in Jones’s reign, Dylan Hartley must share the leadership duties with Owen Farrell after the pair were named co-captains.
Ben Morgan makes his first appearance in an England squad since the 2015 World Cup as a result of the crisis at No 8 that has seen Billy Vunipola and Sam Simmonds ruled out of the entire series by injury and Nathan Hughes miss all but the final match due to suspension.
Jones said: “I’m really happy with the squad. We can only control what we can control and injuries have happened.
“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 have named Dylan and Owen as co-captains for the series. They have both been excellent captains for England in the past and will provide a powerful leadership base for us on and off the field.”
Wing Chris Ashton is present despite having yet to make his debut for Sale with his seven-week ban for a tip-tackle having just elapsed.
Manu Tuilagi has overcome a succession of injuries to win inclusion and he will be competing with Ben Te’o - who has not played this season because of thigh and ankle problems - for selection in midfield.
England’s loose-head prop resources have been decimated by Mako Vunipola’s absence due to a calf issue and the international retirement of Joe Marler, leaving Alex Hepburn and Ben Moon as the only recognised options in the position.
The squad contains eight uncapped players and confirms the decline of veterans Dan Cole and James Haskell, who have been omitted once more.
The final autumn series before the 2019 World Cup is opened by the Springboks’ visit to Twickenham on November 3.
“South Africa have been going really well. They have a new coach and have selected well,” said Jones, whose England team fell to a 2-1 series defeat to Rassie Erasmus’ men in June.
“They play a traditional Springbok game up front and move the ball wide when they need to. We’ll need to take them on up front and when we have opportunities to score points we have to be good enough to take them.”
England squad for next month’s Quilter Internationals – Forwards (20): T Curry (Sale Sharks), C Ewels (Bath Rugby), J George (Saracens), D Hartley (Northampton Saints, co-capt), A Hepburn (Exeter Chiefs), T Hill (Worcester Warriors), M Itoje (Saracens), G Kruis (Saracens), C Lawes (Northampton Saints), Z Mercer (Bath Rugby), B Moon (Exeter Chiefs), B Morgan (Gloucester Rugby), M Rhodes (Saracens), N Schonert (Worcester Warriors), B Shields (Wasps), K Sinckler (Harlequins), E Stooke (Bath Rugby), S Underhill (Bath Rugby), H Williams (Exeter Chiefs), M Wilson (Newcastle Falcons). Backs (16): C Ashton (Sale Sharks), M Brown (Harlequins), D Care (Harlequins), J Cokanasiga (Bath Rugby), E Daly (Wasps), N Earle (Harlequins), O Farrell (Saracens co-capt), G Ford (Leicester Tigers), A Lozowski (Saracens), J May (Leicester Tigers), J Nowell (Exeter Chiefs), H Slade (Exeter Chiefs), B Te’o (Worcester Warriors), M Tuilagi (Leicester Tigers), R Wigglesworth (Saracens), B Youngs (Leicester Tigers).