Reedus was born in Hollywood, Florida and months later moved to Los Angeles, California. Leaving home at the early age of twelve, he has lived in many countries including England, Spain and Japan. He was first discovered at a party in L.A. While in Los Angeles, he worked at a Harley Davidson shop in Venice and at the same time contributed artwork to various shows as a painter, photographer, sculptor, and video artist. He got his first taste of acting in the play "Maps for Drowners" at the TiffanyTheater on Sunset Boulevard.

Reedus is best known for playing the role of Murphy MacManus in the cult movie "The Boondock Saints", written and directed by Troy Duffyand starring opposite Sean Patrick Flaneryand Willem Dafoe He has confirmed returning for the sequel The Boondock Saints II: All Saints Day which started filming in the summer of 2008. He has had roles in Floating, Six Ways to Sunday, Deuces Wild, Blade II, Gossip, Mimic, 8mm, American Gangster, Hero Wanted and Moscow Chill.

On July 25th, 2009, Reedus appeared at Comicon 2009 with other members of The Boondock Saints II: All Saints Day cast and crew to promote the film.

Reedus lives in New York with his son Mingus Lucien Reedus; Mingus's mother is his ex-girlfriend, model Helena Christensen Mingus is named after the legendary jazz musician Charles Mingus.

In 2003 Reedus was injured in a car accident after attending an R.E.M. concert. He had to undergo surgery on the left side of his face that left only a thin scar above his left eyebrow.

He has modeled for Prada, Allesandro Delaqua, and Durban. He currently shows his art work in galleries in New York, Berlin and Frankfurt.