The eldest of three, he was born and raised in New York City's Harlem. He worked for John Hancock Insurance as a life insurance agent in Poughkeepsie, New York, while pursuing his acting career, starring in several stage productions in the New Paltz, New York, locale. His stage surname "Denison" was taken from his friend Jan Denison during his days as an actor and Director at a nonprofit theater in the late 1970s.

Denison is most recently known for his role as Detective Andy Flynn in The Closer (2005–12) and its spin-off Major Crimes (2012–2018). He is well known for his role as mob boss Ray Luca on the NBC crime drama Crime Story (1986–88). Afterwards, he starred and guest-starred in several crime movies and television programs, notably as undercover agent John Henry Raglin in Wiseguy (1987–90), The Great Escape II: The Untold Story (1988), City of Hope (1991), as Joey Buttafuoco in The Amy Fisher Story (1993), as John Gotti in Getting Gotti (1994), Criminal Passion (1994), and as head coach Mike George in ESPN's drama series Playmakers (2003). He appeared in Season 1, Episode 3, of Charmed (1998-2006) as the father of the Halliwell sisters. In 2005, he appeared on Criminal Minds as Sgt. Weigart. He played Detective Buroughs in Karla (2006). He had a recurring role as Aldo Burrows on the Fox series Prison Break (2005–09). In 2000, he played the role of a killer for hire in Walker, Texas Ranger (1993-2001). Denison embodied "Government Investor" in the 2011 Frankie Muniz superhero caper Pizza Man.