The series, called Family Tree, will star Bridesmaids' Chris O'Dowd and will be filmed in the mockumentary style Guest has previously employed in his films Best in Show, Waiting for Guffman and A Mighty Wind.
O'Dowd will play Tom Chadwick, a 30-year-old who begins researching his family history after losing his job and breaking up with his girlfriend. Prompted by a strange box he inherits from a great-aunt he's never met, Tom "uncovers a world of unusual stories and characters" from his past, THR reports.
Guest created the project with partner Jim Piddock, and both will executive-produce and star in the series.
The series will begin casting immediately, and a premiere date has not been set.