Crawford was born in Philadelphia, Pennsylvania, to Lester Crawford and Helen Broderick, who were both vaudeville performers, as his grandparents had been. Lester appeared in films in the 1920s and 1930s. Helen had a career in Hollywood comedies, including a memorable appearance as Madge in the classic musical Top Hat and as Mabel Anderson in the Fred Astaire and Ginger Rogers film Swing Time.

He played his first serious character as a footballer in She Loves Me Not at the Adelphi Theatre, London in 1932. Crawford was originally stereotyped as a fast-talking tough guy early in his career and often played villainous parts.

Crawford made his film debut for Sam Goldwyn in Woman Chases Man (1937). He was in Start Cheering (1938) at Columbia but missed out on reprising his stage performance as Lenny in the film version of Of Mice and Men, losing it to Lon Chaney Jr.

After appearing in Island of Lost Men (1939), Crawford had a Beau Geste style role in The Real Glory (1939). He appeared in two films for Walter Wanger and Tay Garnett, Eternally Yours (1939) and Slightly Honorable (1939).

Crawford married three times. His first marriage was to Actress Kay Griffith in 1940; the couple had two sons together, Christopher Broderick Crawford (1947-2002) and Kelly Griffith Crawford (1951–2012). Through his elder son, Christopher, Crawford has one grandchild, Katherine Lee Crawford (born 1970). Crawford's second marriage was to Joan Tabor in 1962; they divorced in 1967. His third and final marriage, which lasted until Crawford's death in 1986, was to Mary Alice Moore in 1973.

Crawford had one of the leads in South of Tahiti (1941) and North to the Klondike (1941). He supported Edward G. Robinson in Larceny, Inc. (1942) and George Raft in Broadway (1942), and co-starred with Robert Stack in Men of Texas (1942) and Constance Bennett in Sin Town (1942).

During World War II Crawford enlisted in the United States Army Air Corps. Assigned to the Armed Forces Network, he was sent to Britain in 1944 as a sergeant, he served as an announcer for the Glenn Miller American Band. He was one of two announcers on Miller's weekly program I Sustain The Wings, prior to Miller and the band being shipped to England.

He returned to films with roles in Black Angel (1946), a film noir and Slave Girl (1947) with Yvonne de Carlo.

Crawford made he Flame (194) for Republic, and The Time of Your Life (1948) for James Cagney's company. He went back to Paramount for Sealed Verdict (1948) and had a co-starring role in Bad Men of Tombstone (1949) for the King Brothers.

In 1949, Crawford reached the pinnacle of his acting career when he was cast as Willie Stark, a character inspired by and closely patterned after the life of Louisiana Politician Huey Long, in All the King's Men, a film based on the popular novel by Robert Penn Warren. The film was a huge hit, and Crawford's performance as the bullying, blustering, yet insecure Governor Stark won him the Academy Award for Best Actor.

Throughout his adult life, Crawford was prone to bouts of heavy alcohol consumption, and was known for eating large meals. These habits contributed to a serious weight gain for Crawford during the 1950s. His weight and penchant for heavy drinking contributed to several injuries suffered on the set of Highway Patrol. It became particularly difficult for Crawford to perform certain scenes, such as when he had to enter and exit a police helicopter. In 1958, Crawford broke his ankle while exiting the helicopter and was forced to wear an ankle cast, which may be seen in some episodes.

Crawford starred in The Mob (1951), a crime drama. Under the direction of Phil Karlson he starred in Scandal Sheet (1952), based on a novel by Sam Fuller.

MGM borrowed him to play the villain in Lone Star (1952), opposite Clark Gable and Ava Gardner. He went to Warners to star in a comedy, Stop, You're Killing Me (1952).

Crawford returned to Columbia to star in some Westerns, Last of the Comanches (1953), and The Last Posse (1954). 20th Century Fox borrowed him to co-star with Gregory Peck in Nunnally Johnson's Night People (1954).

Crawford was reunited with Glenn Ford in Human Desire (1954), directed by Fritz Lang. Edward Small used him in Down Three Dark Streets (1954) and New York Confidential (1955).

In 1955, television Producer Frederick Ziv of ZIV Television Productions offered Crawford the lead role as "Dan Mathews" in the police drama Highway Patrol, which dramatized law enforcement activities of the California Highway Patrol (CHP). ZIV Television Productions operated on an extremely low budget of $25,000 per episode of Highway Patrol with ten percent of gross receipts going to Crawford as per his contract. While the show's scripts were largely fictional, the use of realistic dialogue and Crawford's convincing portrayal of a hard-as-nails police official helped make the show an instant success. Highway Patrol remained popular during its four years (1955–1959) of first-run syndication, and would continue in repeat syndication on local stations across the United States for many years after. For much of the period from 1955 until 1965 most of Crawford's television roles involved ZIV Television, which was among the relative handful of producers willing to accept the occasional challenges inherent with working with the hard-living and hard-drinking Crawford. Years later, Frederick Ziv admitted in an interview, "To be honest, Broderick could be a handful!"

During the series' run he appeared in The Fastest Gun Alive (1956) with Ford at MGM, a successful Western; Between Heaven and Hell (1956) with Robert Wagner at Fox, directed by Richard Fleischer; and The Decks Ran Red (1958) with James Mason for Andrew L. Stone.

Fed up with the show's hectic shooting schedule, Crawford quit Highway Patrol at the end of 1959 in order to make a film in Spain, and try to get his drinking under control.

Crawford relocated to Europe where he starred in Vittorio Cottafavi's La vendetta di Ercole (1960), known in the U.S. as Goliath and the Dragon.

Crawford's successful run as Dan Mathews in Highway Patrol earned him some two million dollars under his contract with ZIV, who eventually paid him in exchange for Crawford's agreement to sign for the pilot and subsequent production of a new ZIV production, King of Diamonds. Recently back from Europe, and having temporarily stopped drinking, Crawford was signed to play the starring role as Diamond industry security chief John King. King of Diamonds was picked up for syndication in 1961, but ran for only one season before being cancelled. In 1962, after the end of King of Diamonds, Crawford returned to acting in motion pictures: Square of Violence (1962); Convicts 4 (1962); Javier Setó's The Castilian (1963); A House Is Not a Home (1964); Up from the Beach (1965); Kid Rodelo (1966); The Oscar (1966); The Texican (1966) with Audie Murphy; The Vulture (1967); Red Tomahawk (1967).

After 1970, Crawford again returned to television. From 1970–71, he played the role of Dr. Peter Goldstone in The Interns.

Crawford is mentioned in the 1977 film Smokey and the Bandit in the scene where a patrol officer angrily confronts Sheriff Buford T. Justice (Jackie Gleason) and his damaged vehicle. When Justice starts to introduce himself, the trooper interrupts him and barks, "I don't care if your name is Broderick Crawford!"

His last role was as a film Producer who is murdered in a 1982 episode of the Simon and Simon television series. The actor who played the part of the suspected murderer was Stuart Whitman, who had played the recurring part of Sergeant Walters on Highway Patrol.

He died following a series of strokes in 1986 at the age of 74 in Rancho Mirage, California. He has two stars on the Hollywood Walk of Fame, one for motion pictures at 6901 Hollywood Boulevard and another for television at 6734 Hollywood Boulevard.