The Irish star's project for the US cable network - developed with This Is Spinal Tap's Christopher Guest - has been ordered to series, Entertainment Weekly reports.
Family Tree - a mockumentary like much of Guest's past work - will focus on a man (O'Dowd) who is searching for his long-lost relatives and stumbles across a string of unusual characters and stories.
Guest will executive produce the series with Jim Piddock (The Five-Year Engagement), with both men also expected to appear in the show.
IT Crowd actor O'Dowd is best known to US audiences for his role in film comedy Bridesmaids and will next be seen in Sky1 comedy Moone Boy.
Guest's last project was an unaired US remake of BBC comedy The Thick of It in 2007, while his most recent film was 2006's For Your Consideration.
Family Tree will air on HBO in the US and on BBC Two in the UK, as part of a co-production deal.