Willard, McKean and Begley have appeared in Guest's mockumentary films in the past, including Best in Show and A Mighty Wind.
The trio have landed recurring roles in Guest's new HBO series, which stars Chris O'Dowd as a man investigating his family's mysterious past.
McKean is to play Tom's (O'Dowd) father in Family Tree, with Begley portraying Tom's Uncle Andy.
Willard has signed for the role of Andy's eccentric neighbour Mike, according to The Hollywood Reporter.
Don Lake will also appear in a guest role in Family Tree.
The sitcom's pilot will be directed by Guest, who is also executive producing Family Tree with Jim Piddock (The Five-Year Engagement).
Family Tree - which is expected to follow Guest's mockumentary style- is to air on BBC Two in the UK as well on HBO in the US.
Watch a trailer for A Mighty Wind below: