The Nottinghamshire batsman has been one of the world's highest-ranked Twenty20 players for a couple of years and his recent domestic form has now earned him an opportunity in a longer format.
There is no place, however, for Essex all-rounder Ravi Bopara, who has held a regular place in England's recent limited-overs sides, while Stuart Broad will sit out of the five matches to rest his facial injury.
The inclusion of Hales does not spell the end of Ian Bell's one-day career, with Alastair Cook's usual opening partner, along with another experienced figure in James Tredwell, retained in the 15-man party.
The series begins next Monday at Bristol, with India looking to bounce back from their 3-1 Test series defeat.
England squad: Cook (c), Ali, Anderson, Ballance, Bell, Buttler [wkt], Finn, Gurney, Hales, Jordan, Morgan, Root, Stokes, Tredwell, Woakes.