Deayton will front six-part series, It's Your Round, in which guests such as Miles Jupp, Arthur Smith and Rebecca Front invent their own rounds for the show, reports The Guardian.
The programme, which will premiere on February 17 at 11pm, marks Deayton's first comedy series on Radio 4 since the award-winning Radio Active in the 1980s.
After Radio Active transferred to BBC Two as KYTV, Deayton took on various television roles, including an acting part in comedy One Foot In the Grave.
He was also the long-running host of current affairs panel show Have I Got News For You, but left the programme in 2002 after tabloid allegations about his private life.
Deayton returned to the BBC in 2003 to guest star as a spin-doctor in an episode of political comedy Absolute Power, followed by a role in BBC sitcom Nighty Night from 2004.
Next year, Radio 4 will offer more comedy programming to its listeners, including a new podcast titled Comedy of the Week: Mondays Don't Have to be Miserable.
The station will also air an improvisation show called Showstopper! The Improvised Musical, starring Pippa Evans, Ruth Bratt, Sean McCann and others.