Hudlin was born in Centreville, Illinois, the son of Helen (née Cason), a teacher, and Warrington W. Hudlin, Sr., an insurance executive and teacher. His older brother, Warrington Hudlin, is also a film director, as well as an actor and producer.
While an undergraduate student at Harvard University, Hudlin directed a short film entitled, "House Party," which went on to receive numerous awards including first place at the Black American Cinema Society Awards. It would serve as the basis for his first feature film of the same name.
From 2005 to 2008, Hudlin was the President of Entertainment for BET. He was the writer of the Marvel Comics series Black Panther from 2005 to 2008, most notable for the 2006 storyline "Bride of the Panther," which saw the characters Storm and the Black Panther wed.
Reginald Hudlin is a member of Phi Beta Sigma fraternity.