Norman Reedus was born in Hollywood, Florida. He is of Italian, English, Scottish and Irish descent. He is an accomplished photographer with several books of his photography published and continues to do art shows in galleries all around the world every year. His first novel was published in 2022 and was on the New York Times best seller list as well as the Los Angeles Times best seller list titled "The Ravaged". Reedus has a production company named Bigbaldhead, Inc. With his producing partner Amanda Verdon as well as a first look deal with AMC studios.

Norman's first movie as an actor was Guillermo del Toro's horror thriller Mimic (1997), where he played the character Jeremy. He has also played roles in the movies Floating (1997), Six Ways to Sunday (1997), Gossip (2000), Blade II (2002) and Deuces Wild (2002). He also starred in the movies Red Canyon (2008), Robert Redford's The Conspirator (2010), and John Hillcoat's Triple 9 (2016). Norman played the role of Murphy MacManus in the movie The Boondock Saints (1999) opposite Sean Patrick Flanery and Willem Dafoe. He later reprised the role in the sequel The Boondock Saints II: All Saints Day (2009).

His directorial debut happened in 2005 for the multi-awarded short film on Miles Davis I Thought of You (2006).

As of 2010, he stars as Daryl Dixon on the AMC television series The Walking Dead (2010). The character was not originally in the comic book series of the same name, but was created specifically for Reedus by Frank Darabont. The Walking Dead comic creator Robert Kirkman has stated he 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 great deal of Norman'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."