According to Bill Georgaris of They Shoot Pictures, Don't They,[citation needed] Cook appeared in 21 films noir, more than any other actor or actress.

He played cheerful, brainy collegiates until he was cast against type as the bug-eyed baby-faced killer Wilmer Cook in the 1941 version of The Maltese Falcon.

Cook's acting career spanned more than 60 years, with roles in productions including The Big Sleep, Shane, The Killing, House on Haunted Hill and Rosemary's Baby.

[11][12] In 1930, Cook traveled to California, where he made his film debut in Hollywood's version of the play Her Unborn Child, a motion picture directed by Albert Ray and produced by Windsor Picture Plays Inc.[13] At Twentieth Century-Fox, Cook made an impression as a bespectacled college freshman with radical ideas in the musical comedy Pigskin Parade (1936).

He did return to Fox occasionally in prominent roles: as a songwriter in the Alice Faye-Betty Grable musical Tin Pan Alley (1940), and as a mobster disguised as an old woman in the Laurel and Hardy feature A-Haunting We Will Go (1942).

[citation needed] In addition to his performance as Wilmer in The Maltese Falcon (1941), some of Cook's other notable roles include the doomed informant Harry Jones in The Big Sleep (1946), the henchman (Marty Waterman) of the murderous title character in Born to Kill (1947), the pugnacious ex-Confederate soldier 'Stonewall' Torrey who is gunned down by Jack Palance in Shane (1953), and George Peatty, the shady, cuckolded husband in Stanley Kubrick's The Killing (1956).

Other films in which he appeared are William Castle's horror film House on Haunted Hill (1959), One-Eyed Jacks (1961), Papa's Delicate Condition (1963), Blood on the Arrow (1964), Rosemary's Baby (1968), The Great Bank Robbery (1969), El Condor (1970), Blacula (1972), The Great Northfield Minnesota Raid (1972), Pat Garrett and Billy the Kid (1973), The Outfit (1973), Tom Horn (1980), and Treasure: In Search of the Golden Horse (1984).

He played a private detective, Homer Garrity, in an episode of Adventures of Superman television series titled "Semi-Private Eye," airing for the first time on January 16, 1954.

Cook portrayed lawyer Samuel T. Cogley in the Star Trek 1967 episode "Court Martial",[14] Isaac Isaacson on the Batman television series, Weasel Craig in Salem's Lot, and later had a long-term recurring role as Honolulu crime lord "Ice Pick" on CBS's Magnum, P.I.

[1] According to John Huston, who in 1941 directed him in The Maltese Falcon: [Cook] lived alone up in the High Sierra, tied flies and caught golden trout between films.