Waldo Brian Donlevy was born in Portadown, County Armagh in 1901. Sometime between 1910 and 1912 the family moved to Sheboygan Falls, Wisconsin, where Donlevy's father worked as a supervisor at the Brickner Woolen Mills. When the local Army National Guard company was called into service for the Pancho Villa Expedition in 1916, Donlevy lied about his age (he was actually 14) so he could join the mobilization. Donlevy served during the expedition as a bugler. When the United States entered World War I, Donlevy went to France with Company C, 127th Infantry Regiment, a part of the 32nd Infantry Division.
Donlevy began his career in New York in the early 1920s, appearing in many theater productions and also winning an increasing number of silent film parts. Previously, he had modeled for the illustrator J.C. Leyendecker, who produced illustrations for the famous Arrow Collar advertisements. His Broadway credits included Hit the Deck and Life Begins at 8:40.
Donlevy's break came in 1935, when the bull-necked Irishman was cast in the Edward G. Robinson film Barbary Coast. A large amount of film work followed, with several important parts. In 1939, he played the lead villain in Destry Rides Again and was nominated for an Academy Award for Best Supporting Actor for his memorable role as the ruthless Sergeant Markoff in Beau Geste, although the Oscar went to the sentimental choice, Thomas Mitchell for Stagecoach.
The following year, he played the role for which he is perhaps best remembered, that of McGinty in The Great McGinty, a role he reprised four years later in The Miracle of Morgan's Creek. In 1942, Donlevy starred in Wake Island with William Bendix and Robert Preston and played street-tough borough politician Paul Madvig in Dashiell Hammet's classic The Glass Key. In 1955, he played the lead in the British science-fiction horror film The Quatermass Xperiment (called The Creeping Unknown in the US) for the Hammer Filmscompany, playing the lead role of Professor Bernard Quatermass. The film was based on a 1953 BBC Television serial of the same name. The character had been British, but Hammer cast Donlevy in an attempt to help sell the film to North American audiences. Quatermass creator Nigel Kneale disliked Donlevy's portrayal, referring to Donlevy as "a former Hollywood heavy gone to seed". Nonetheless, the film version was a success and Donlevy returned for the sequel, Quatermass 2 (Enemy From Space in the US), in 1957, also based on a BBC television serial. This made Donlevy the only man ever to play the famous scientist on screen twice, although later Scottish actor Andrew Keir would play him two times, once on film and then on the radio.
Throughout his film career, Donlevy also did several radio shows, including a reprise of The Great McGinty. He played the lead character in Dangerous Assignment between 1949 and 1954, taking the series to TV in 1952. He featured in a number of films over the following years until his death. He also appeared in a variety of television series from the late 1940s until the mid-1960s, guest-starring on such popular programs as Crossroads, Perry Mason, Wagon Train and Rawhide,. In 1957, he appeared in a CBS production of the A. J. Cronin's Beyond This Place. In 1960, he appeared as John Ridges in the episode "Escape" of CBS's anthology series The DuPont Show with June Allyson, with Sylvia Sidney portraying his wife. His last film role was in The Winner, released in 1969.
Donlevy was married three times: first to Yvonne Grey from 1928–36, then to actress Marjorie Lane from 1936–1947, and finally to Lillian Arch Lugosi (the ex-wife of Bela Lugosi, famous for playing Dracula) from 1966 until his death in 1972.
Donlevy died from throat cancer on April 5, 1972 at the Motion Picture Country Hospital in Woodland Hills, California. He was survived by his wife and a daughter, Judy Donlevy, by his second wife. His ashes were scattered over Santa Monica Bay.