Norman Reedus made his debut in the 1997 American drama film ‘Floating’ where he played the role of ‘Van.’ The same year, he also appeared in the American science fiction horror film ‘Mimic’ directed by Guillermo del Toro. The film opened to a mixed critical reception and was a commercial failure. He went on to star in films like ‘I'm Losing You’ (1998), ‘Reach the Rock’ (1998), ‘Let the Devil Wear Black’ (1999), ‘8mm’ (1999), ‘The Boondock Saints’ (1999), ‘Beat’ (2000), ‘Gossip’ (2000), ‘Sand’ (2000), and ‘Luster’ (2002). In 2002, he starred as 'Scud' in the American superhero horror film ‘Blade II’ directed by Guillermo del Toro. The film, despite receiving mixed reviews, was a commercial success and grossed over $155 million on a $54 million budget. That same year, he also portrayed Marco Vendetti in the Scott Kalvert-directed American crime drama film ‘Deuces Wild.’ The film was panned by critics and was a commercial failure. He next starred in films like ‘Octane’ (2003), ‘Until the Night’ (2004), ‘Antibodies’ (2005), ‘The Notorious Bettie Page’ (2005), ‘A Crime’ (2006), ‘American Gangster’ (2007), ‘Moscow Chill’ (2007), ‘Red Canyon’ (2008), ‘Cadillac Records’ (2008), ‘Pandorum’ (2009), and ‘The Boondock Saints II: All Saints Day’ (2010).
In 2010, he joined the main cast of the American post-apocalyptic horror television series ‘The Walking Dead’ developed by Frank Darabont. He played the role of ‘Daryl Dixon’ in the show which earned him several awards including the ‘Saturn Award’ and ‘IGN Award.’ The eleventh and final season premiered in August 2021. He starred as ‘Lax Morales’ in the 2011 American drama film ‘Hello Herman’ directed by Michelle Danner. The film saw mostly negative reviews upon release and received a 20% approval rating on Rotten Tomatoes. In 2013, he appeared in the Laurie Collyer-directed American drama film ‘Sunlight Jr.’ The film received mostly positive reviews from critics. He continued to star in films like ‘Stretch’ (2014), ‘Vacation’ (2015), ‘Air’ (2015), ‘Sky’ (2015), and ‘Triple 9’ (2016). In 2016, he became a part of the American travel series ‘Ride with Norman Reedus’ as a host. The series ran for 5 seasons and aired its final episodes in April 2021. He was last seen in the Episode: "Daryl's Story" of the television series ‘The Walking Dead: Origins’ in 2021.