Born and raised in White Plains, New York, Duryea graduated from White Plains Senior High School in 1924 and Cornell University in 1928. While at Cornell, Duryea was elected into the prestigious Sphinx Head Society, Cornell's oldest senior honor society. He majored in English with a strong interest in drama, and in his senior year succeeded Franchot Tone as president of the college drama society.
As his parents did not approve of his choice to pursue an acting career, Duryea became an advertising executive but after six stress-filled years, had a heart attack that sidelined him for a year.
Returning to his earlier love of acting and the stage, Duryea made his name on Broadway in the play Dead End, followed by The Little Foxes, in which he portrayed Leo Hubbard. In 1940, Duryea moved to Hollywood to appear in the film version of The Little Foxes. He continued to establish himself with supporting and secondary roles in films such as The Pride of the Yankees and None But the Lonely Heart. As the 1940s progressed, he found his niche as the "sniveling, deliberately taunting" antagonist in a number of film noirsubjects: (Scarlet Street, The Woman in the Window, Criss Cross, Too Late for Tears) and westerns such as Winchester '73, although he was sometimes cast in more sympathetic roles (Black Angel, Ministry of Fear, One Way Street). In 1946, exhibitors voted him the eighth most promising "star of tomorrow".
When interviewed by Hedda Hopper in the early 1950s, Duryea spoke of career goals and his preparation for roles: "Well, first of all, let's set the stage or goal I set for myself when I decided to become an actor ... not just 'an actor', but a successful one. I looked in the mirror and knew with my "puss" and 155-pound weakling body, I couldn't pass for a leading man, and I had to be different. And I sure had to be courageous, so I chose to be the meanest s.o.b. in the movies ... strictly against my mild nature, as I'm an ordinary, peace-loving husband and father. Inasmuch, as I admired fine actors like Richard Widmark, Victor Mature, Robert Mitchum, and others who had made their early marks in the dark, sordid, and guilt-ridden world of film noir; here, indeed, was a market for my talents. I thought the meaner I presented myself, the tougher I was with women, slapping them around in well produced films where evil and death seem to lurk in every nightmare alley and behind every venetian blind in every seedy apartment, I could find a market for my screen characters."
"At first it was very hard as I am a very even-tempered guy, but I used my past life experiences to motivate me as I thought about some of the people I hated in my early as well as later life ... like the school bully who used to try and beat the hell out of me at least once a week ... a sadistic family doctor that believed feeling pain when he treated you was the birthright of every man inasmuch as women suffered giving birth ... little incidents with trade-people who enjoyed acting superior because they owned their business, overcharging you. Then the one I used when I had to slap a woman around was easy! I was slapping the over-bearing teacher who would fail you in their 'holier-than-thou' class and enjoy it! And especially the experiences I had dealing with the unbelievable pompous 'know-it-all-experts' that I dealt with during my advertising agency days ... almost going 'nuts' trying to please these 'corporate heads' until I finally got out of that racket!"
In his last years, Duryea worked in overseas film productions including the Italian Western, The Hills Run Red (1966) and the spy thriller Five Golden Dragons (1967) in West Germany while continuing to find roles on American television. He also appeared twice on the big screen with his son, character actor Peter Duryea, in the low-budget Westerns Taggart (1964) and The Bounty Killer (1965).
Duryea starred as the lead character China Smith in the television series China Smith from 1952 to 1956; and The New Adventures of China Smith from 1953 to 1954.
Duryea guest starred as Roy Budinger, the self-educated mastermind of a criminal ring dealing in silver bullion, in the episode "Terror Town" on October 18, 1958 of NBC's western series Cimarron City.
In 1959, Duryea appeared as an alcoholic gunfighter in third episode of The Twilight Zone, "Mr. Denton on Doomsday". He guest starred on NBC'santhology series The Barbara Stanwyck Show and appeared in an episode of Rawhide in 1959, "Incident Of The Executioner." On September 15, 1959, Duryea guest starred as the outlaw Bud Carlin in the episode "Stage Stop", the premiere of NBC's Laramie western series. Duryea appeared again as Luke Gregg on Laramie on October 25, 1960, in the episode "The Long Riders". \
Three weeks later, on November 16, 1960, Duryea played a mentally unstable pioneer obsessed by demons and superstitions in "The Bleymier Story" of NBC's Wagon Train. Duryea was cast twice in 1960 as Captain Brad Turner in consecutive episodes of the NBC western series Riverboat.
In 1963, Duryea portrayed Dr. Ben Lorrigan on NBC's medical drama, The Eleventh Hour. From 1967 to 1968, he appeared in a recurring role as Eddie Jacks on the soap opera Peyton Place.
Duryea was quite different from the unsavoury characters he often portrayed. He was married for 35 years to his wife, Helen, until her death in January 1967. The couple had two sons: Peter (who worked for a time as an actor), and Richard, a talent agent. At home, Duryea lived a quiet life at his house in the San Fernando Valley, devoting himself to gardening, boating and community activities that included, at various times, active membership in the local parent-teacher association and command of a Boy Scout troop.
On June 6, 1968, Duryea died of cancer at the age of 61. The New York Times tellingly noted the passing of a "heel with sex appeal". His remains are interred in Forest Lawn - Hollywood Hills Cemetery in Los Angeles, California.