Gambon left school at age 15 and worked in a factory sweeping floors and serving tea to the workers before being bitten by the acting bug. He made his first stage appearance in 1962 as "the second gentleman" in a Dublin production of "Othello". Gambon then went to London where he performed (usually in spear carrier roles) at the National Theatre under the tutelage of Laurence Olivier. At Olivier's suggestion, Gambon also worked at the Birmingham Repertory Theatre to gain more experience which eventually led to his becoming a leading stage actor in Britain. Gambon played Roderigo in an acclaimed National Theatre production of "Othello" from 1978-80. After winning praise for his "Galileo" in 1980, the hulking actor was dubbed 'the Great Gambon' by Sir Ralph Richardson. On stage, Gambon has had a long association with playwright Alan Ayckbourn, including "The Norman Conquests" (1974-75), "Just Between Ourselves" (1977), "A Chorus of Disapproval" (1985), "A Small Family Business" (1987) and "Man of the Moment" (1990-91). After earning raves and winning several awards for his portrayal of Eddie in the 1987 revival of Arthur Miller's "A View From the Bridge", he co-starred with Jack Lemmon in the 1989 world premiere of Donald Freed's "Veteran's Day" in London's West End. He has remained a constant theatrical presence into the 90s, including an award-winning turn as "Volpone" (1995).

Gambon's early TV work included playing a religious alongside Trevor Howard and Martin Sheen in "Catholics" (CBS, 1973), but he is best recalled for both "Maigret" and "The Singing Detective". Although he began working on the big screen in 1974 with "The Beast Must Die," it was not until well into the 80s that Gambon began getting significant roles. He was the man from Charlotte Rampling's past in David Hare's "Paris By Night" (1988), the magistrate opposite Marlon Brando in Euzhan Palcy's "A Dry White Season" (1989), Robin Williams' crazy militaristic uncle in "Toys" (1992), and the upper crust Brit who brings an American Indian across the Atlantic in "Squanto: A Warrior's Tale" (1994). In 1996, Gambon provided the voice of Badger for the animated feature based on the classic children's novel, "The Wind in the Willows" and played Julia Roberts' father in "Mary Reilly.”

In 1999, Gambon portrayed the CEO of Brown and Williamson Tobacco in the controversial movie "The Insider" before starring in the London production "Cressida" (2000). In 2002, Gambon deftly breathed vitality and emotion into the life of President Lyndon B. Johnson in the HBO drama "A Path To War", which received an Emmy nomination. His next major role was as a menacing frontier sheriff in actor/director Kevin Costner's Western opus "Open Range" (2003), followed by turns in the Sylvia Plath biopic "Sylvia" (2003) starring Gwyneth Paltrow and the acclaimed HBO miniseries "Angels in America" (2003). After that Gambon was tapped to ably succeed the late Richard Harris in the role of Professor Albus Dumbledore in "Harry Potter and the Prisoner of Azkaban" (2004). He had a small role in the ambitious, but fatally-flawed live action-CGI blend, “Sky Captain and the World of Tomorrow” (2004), then appeared as a documentary producer for a team of underwater adventurers in Wes Anderson’s depthless comedy, “The Life Aquatic with Steve Zissou” (2004).

Gambon was soon tapped by first-time director Matthew Vaughn for his slick crime drama, “Layer Cake” (2005), wherein he played a big time crime boss whose missing daughter is tracked by a drug dealer (Daniel Craig) looking to retire. After playing a supporting role in “Ladies in Lavender” (2004), a nostalgic period drama about two elderly sisters (Maggie Smith and Judi Dench) living in a coastal town outside Cornwall whose peaceful lives are put at odds when a young German man (Daniel Brühl) washes ashore, Gambon reprised his role as Professor Dumbledore in “Harry Potter and the Goblet of Fire” (2005), the first installment to be helmed by a British director (Mike Newell).