Kelly, one of seven children, was born in Detroit, Michigan, the son of Margaret and Robert Corby Kelly, a painter and art instructor who retired as an accountant for the Avon Tubing Company. He is well-known for playing Luther in the 1979 cult film The Warriors, where he screeches the famous line, "Warriors... come out to play-ee-ay!!"; he also played a character named Luther in the 1982 hit film 48 Hrs.
His film credits include Commando, Crooklyn, Hammett, Wild at Heart, The Crow, Dreamscape, The Adventures of Ford Fairlane, Last Man Standing, "Songcatcher", K-PAX, The Longest Yard, and Flags of Our Fathers.
His largest television role was Jerry Horne on Twin Peaks; his television guest appearances include Miami Vice, Moonlighting, Spenser: For Hire, Ghostwriter, Third Watch, Hack, Kidnapped, and Law & Order.
Onstage Kelly has played some of the greatest roles in the World Classical canon on Broadway and at leading theatres throughout the USA. He has frequently appeared at the Hartford Stage Company in Hartford, Connecticut starring in the title roles in Woyzeck and Tartuffe, playing Iago in Othello and Hoss in Sam Shepard's Tooth Of Crime. At the American Repertory Theatre in Cambridge, Massachusetts, he played the title role in Pirandello's Enrico IV and starred in an adaption of the Yuan Dynasty Chinese classic Snow In June. On Broadway he played Feste in the Lincoln Center production of Twelfth Night. He appeared in four plays by avant garde master Richard Foreman: Pearls For Pigs, The Mind King, Film Is Evil/Radio Is Good, and The Cure. In 1998 he received an Obie Award for Sustained Excellence.
As a composer and musician he participated in New York's rock and cabaret scene playing such legendary venues as Max's Kansas City, Reno Sweeney's, CBGB, and The Lower Manhattan Ocean Club. In May 2008 he released a CD of his original music entitled "David Patrick Kelly : Rip Van Boy Man" containing new songs and live recordings from his club days in 1975.
He married theater actress/writer Juliana Francis on August 14, 2005. Kelly is an avid martial artist with a Second Degree Black Belt (Nidan Rank) in Seido Karate and a practitioner of three forms of Tai Chi (Chen, Yang, Palm).