Bowie's first film major role in The Man Who Fell to Earth earned acclaim, as did his performance on stage as The Elephant Man. He had appeared in a few late '60's avant garde films, mostly as an extra. Since then his acting career has been sporadic. Nagisa Oshima's film Merry Christmas, Mr. Lawrence, based loosely on Laurens van der Post's novel The Seed and the Sower, was released in 1983. Bowie played Maj. Jack Celliers, a prisoner of war in a Japanese internment camp; another famous musician, Ryuichi Sakamoto, played the camp commandant. Bowie has a small part as a hit-man in 1985 film Into the Night. Bowie also played a sympathetic Pontius Pilate in Martin Scorsese's The Last Temptation of Christ.

Mr. Lawrence impressed some critics but his next project, the rock musical Absolute Beginners (1986), was both a critical and box office disappointment. The same year he appeared in the Jim Henson movie Labyrinth, playing Jareth, the king of the goblins.

Along with numerous appearances as himself, Bowie also appeared in The Hunger, a revisionist vampire movie with Catherine Deneuve and Susan Sarandon; Basquiat, a biopic of the artist Jean-Michel Basquiat, in which Bowie played Andy Warhol to great acclaim; and as mysterious FBI agent Phillip Jeffries in Twin Peaks: Fire Walk With Me. He also made a cameo appearance as himself in the 2001 comedy Zoolander.

Bowie appears in the 2002 List of "100 Great Britons" (sponsored by the BBC and voted for by the public), alongside such other greats as Winston Churchill and John Lennon.

Bowie has been cast in director Christopher Nolan's project, The Prestige. Bowie will portray Nikola Tesla alongside Batman Begins star: Christian Bale and X-Men 3 star Hugh Jackman.

It is rumoured that Bowie may be cast as The Joker (comics) in Christopher Nolan's 2008 sequel to 2005's Batman Begins.