Lance Reddick made his debut in 1996 in an episode of New York Undercover. In 2000 and 2001 he played the role of detective Johnny Basil in the HBO television series Oz. In 2002 he appeared in the video clip 03 Bonnie & Clyde by Jay-Z and Beyoncé as a police officer. From 2002 to 2008 he starred in the television series The Wire with the role of Cedric Daniels. In 2008-2009, Reddick played Matthew Abaddon on the television series Lost.
Series producers Damon Lindelof and Carlton Cuse wanted him in the series created by Lindelof himself with J. J. Abrams and Jeffrey Lieber after seeing him act in Oz, just as they did for Harold Perrineau, Adewale Akinnuoye-Agbaje and Ken Leung. Also in 2008 he agreed to star in the pilot episode of the series Fringe, created by Abrams himself in the role of Phillip Broyles. He played the role until 2013, when the series came to an end. In 2011 he married Stephanie Day.
In 2014 he was chosen by Ryan Murphy to play the role of Papa Legba in the third season of American Horror Story, a role which he will then resume in 2018, in the eighth season. Also since 2014 he has played the role of Charon, goalkeeper of the Continental in the John Wick film series, until 2023.
On February 22, 2023, he posted his latest unboxing video on Facebook as the official announcement of his participation in the spin-off film Ballerina. On March 17, 2023, at the age of 60, he died of cardiovascular disease at his home in Los Angeles.