Reedus was born in Hollywood, Florida, the son of Marianne (née Yarber), a teacher, and Ira Norman Reedus. He is of English, Irish, Italian, and Scottish descent. He grew up in Los Angeles, California, and also lived in Ireland, Japan, and Spain. He worked at a Harley-Davidson shop in Venice, California, and contributed artwork to various shows as a painter, photographer, sculptor, and video artist. He first acted in the play Maps for Drowners at the Tiffany Theater on Sunset Boulevard. He was discovered at a party in Los Angeles, where someone asked him if he wanted to act in a play.
Reedus' first film was in the 1997 Guillermo del Toro horror thriller film Mimic, where he played the character Jeremy. He also had roles in the films Dark Harbor, Six Ways to Sunday, Deuces Wild, Blade II, Gossip, 8mm, American Gangster, Hero Wanted, and Moscow Chill. In 2005, he had a bit part in the Christian Alvart film Antibodies as a German policeman. In 2008, he starred in the film Red Canyon. Reedus played Murphy MacManus in the 1999 movie The Boondock Saints. He reprised the role in the 2009 sequel The Boondock Saints II: All Saints Day. He guest-starred on Charmed as Paige's (Rose McGowan) boyfriend, Nate. Reedus also starred in the film Hello Herman, which opened nationwide and on-demand on June 7, 2013. Reedus currently stars in the reality series Ride with Norman Reedus, which premiered on June 12, 2016,
In 2010, Reedus began playing Daryl Dixon in the AMC television series The Walking Dead, a horror drama about a group of friends and family members who fight to survive in a violent apocalyptic world populated with flesh-eating zombies and the few surviving humans, some of whom are even more diabolical and dangerous than the zombies themselves. The character was not originally in the comic book series of the same name, but was created specifically for Reedus after his audition for the character of Merle Dixon. The Walking Dead comic creator Robert Kirkman feels "absolutely blessed Reedus has honored the show with his presence, and the way he has come in and taken over that role and defined Daryl Dixon. A lot of Reedus's portrayal of the character in the first season inspired all the writers to do what we did with him in the second season. We love writing him and end up doing cool stuff with him." The drama has evolved into the highest-rated in cable history, smashing all previous records. Reedus was nominated for a 2012 Saturn Award for Best Supporting Actor for his portrayal of Dixon.
Reedus has modeled for Prada, Alessandro Dell'Acqua, Durban, Levi's, Lexus, and Morgenthal Fredrics. In 2015 Reedus posed for a Cruelty Free International ad in support of ending cosmetic tests on animals.
In the mid-1990s, while working as a model, he appeared in the music videos for "Wicked As It Seems" by Keith Richards, "Violently Happy" by Björk, "Flat Top" by Goo Goo Dolls, "Cat's in the Cradle" covered by Ugly Kid Joe, "Strange Currencies" by R.E.M. and "Fake Plastic Trees" by Radiohead. In 1999 he appeared in the video for "Mean to Me" by Tonic. Since achieving fame as an actor, he has also appeared in the videos for "Judas" by Lady Gaga, "Sun Down" by Tricky (ft. Tirzah), "Gypsy Woman" by Hilary Duff and "No Cities to Love" by Sleater-Kinney.
He is also a painter, sculptor, and photographer who currently shows his artwork in galleries in New York City, Berlin, and Frankfurt. He released a book of photography on October 31, 2013, called The Sun's Coming Up... Like A Big Bald Head, and in September 2014 announced a fan art compilation called Thanks For All The Niceness.
He is currently signed with Unsigned Group in London.
Reedus reprised his Walking Dead character of Daryl Dixon in the 2013 video game The Walking Dead: Survival Instinct, which is set within the universe of the television series.
Reedus was to portray the main character in Hideo Kojima and Guillermo del Toro's Silent Hills—a horror game that was to serve as a reboot of the Silent Hill franchise. However, as a result of Kojima's exit from his previous employer, Konami, Silent Hills was effectively cancelled in 2015. Reedus would ultimately resurface in a new Kojima project, Death Stranding.
Reedus was in a five-year relationship with supermodel Helena Christensen from 1998 until 2003. Despite reports to the contrary, the two were never married. Together they have a son, Mingus Lucien Reedus (born October 13, 1999). The two have remained friends and share joint custody of their son.
In February 2005, Reedus sustained a head injury when a truck collided with his car in Germany. His nose was reconstructed with the aid of four screws and his left eye socket with titanium.