Duff was born in Charleston, Washington (today a part of Bremerton), in 1913. He graduated from Roosevelt High School in Seattle in 1932, where he began acting in school plays after he was cut from the school basketball team.
Duff worked locally in Seattle-area theater until entering the United States Army Air Corps during World War II. He was eventually assigned to their radio service, and announced re-broadcasts prepared for the Armed Forces Radio Service (AFRS). In this role, he served as the announcer for the drama Suspense, dated March 16, 1943.
Duff's most memorable radio role was as Dashiell Hammett's private eye Sam Spade in The Adventures of Sam Spade (1946–1950). Due to accusations of Duff being a communist and with his TV and film career starting to take hold, he ultimately left the program in 1950 at the start of its final season; Stephen Dunne took over the voice role of Spade.
Duff was signed to a long-term contract with Universal, and made his film debut alongside Burt Lancaster as an inmate in 1947's Brute Force. The movie was produced by Mark Hellinger and directed by Jules Dassin, who gave Duff a bigger role in their next film, The Naked City (1948). He subsequently reunited with Lancaster for the family drama All My Sons (also 1948), based on the play of the same name by Arthur Miller.
More substantial roles soon followed, with Duff taking the lead in numerous Westerns and films noir including Illegal Entry, Red Canyon, Johnny Stool Pigeon, Calamity Jane and Sam Bass (all 1949);[6]Spy Hunt, Shakedown and Woman in Hiding (all 1950). The latter film saw Duff act alongside his future wife Ida Lupino; the couple would subsequently co-star in a further four films during the 1950s.
In 1951, Duff made a pilot for a new radio series, The McCoy. Following his marriage to Lupino in October 1951, Duff was granted a release from his contract with Universal.
Duff appeared in the 1952 film That Kind of Girl (aka Models Inc), and also featured in Spaceways, and Roar of the Crowd (both 1953), the latter for Monogram Pictures, which ultimately made Jennifer (also 1953), the second movie in which he starred alongside his wife.
His other film appearances beside his wife; Don Siegel's Private Hell 36 (1954); Lewis Seiler's Women's Prison (1955), and Fritz Lang's While the City Sleeps (1956) continued Duff's successful run of movies during the 1950s.
In addition to his movie roles, Duff also experienced success in television, with appearances in the 1950s series The Star and the Story, Climax! and Crossroads. From January 1957 to July 1958, he appeared with Lupino in the CBS sitcom Mr. Adams and Eve, which revolved around the private lives of two fictitious film stars, Howard Adams and Eve Drake, who were married to each other. They also served as producers.
Other TV roles included an appearance in NBC's western series Bonanza, playing a young Samuel Langhorne Clemens in his early life in the West as a satirical and crusading journalist, in the first-season episode "Enter Mark Twain". Duff also featured in episodes of numerous TV series during the 1960s including The Twilight Zone, Burke's Law, Combat, episode “Missing in Action”The Eleventh Hour, Mr. Novak and Batman (the latter in an episode entitled "The Entrancing Dr. Cassandra", alongside wife Ida Lupino). In 1960, Duff portrayed Arthur Curtis on The Twilight Zone in an episode titled “A World of Difference.” In 1963 Duff appeared as Ed Frazer on The Virginian in the episode titled "A Distant Fury."
Duff had the lead role in the short-lived TV series Dante (which ran for only one season; 1960–61), but found greater success as Detective Sergeant Sam Stone in the ABC police drama Felony Squad (1966–69). Duff appeared in all 73 episodes of the series during its three-season run, alongside his co-stars Dennis Cole and Ben Alexander. He also directed one episode; "The Deadly Abductors".
Duff also directed seven episodes of the 1965–1966 television sitcom Camp Runamuck.
Duff died at age 76 of a heart attack on July 8, 1990, in Santa Barbara, California.
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