Standing an imposing 6'4 and featuring a closely shaved head, Duke first became a familiar face to moviegoers in Car Wash (1976) where he portrayed fierce young Black Muslim revolutionary Abdullah Mohammed Akbar (formerly known as Duane), and expanded his repertoire with American Gigolo (1980) as a homosexual (Note: in the film, Duke is seen with hair as opposed to his other films).
As the action-film oriented genre became more popular, Duke's presence was perfect to portray a myriad of 'tough guy' roles, chiefly alongside Arnold Schwarzenegger in Commando and Predator, as well as the memorable police chief in Carl Weathers' action vehicle Action Jackson. He played a detective investigating a murder in Menace II Society with his now classic line "You know you done fucked up now... you know that right." He was a dirty cop in the Mel Gibson revenge movie Payback and has appeared in X-Men: The Last Stand as Bolivar Trask. He also played the role of Levar in the 2005 film Get Rich or Die Tryin'.
He guest starred in the fourth episode of Lost in its third season as Warden Harris, in the episode Every Man for Himself. He also guest starred in Battlestar Galactica in the season two episode Black Market.
Duke was also cast as reoccurring character Capt. Parish in the action television series/crime drama Fastlane (September 18, 2002 – April 25, 2003).