After a stint as an amateur boxer, Dexter attended the Pasadena Playhouse, where he studied acting. He had a small role in The Mortal Storm (1940). During World War II he enlisted for military Service with the U.S. Army Air Corps, where he met and befriended Karl Malden, a fellow Serbian-American, and appeared uncredited in the Corps play and film Winged Victory (1944).

After the war, Dexter had a role in Heldorado (1946), a Roy Rogers western, as "Barry Mitchell". He appeared under this name in Sinbad, the Sailor (1947). He appeared on Broadway in Magnolia Alley (1949).

He eventually changed his name to Brad Dexter and had roles in The Asphalt Jungle (1950) and Fourteen Hours (1951). Dexter's breakthrough role was as a villain in RKO's The Las Vegas Story (1951) with Victor Mature and Jane Russell. RKO cast him in a similar part in Macao (1952) with Russell. RKO signed him to a term contract.

Dexter was villainous to John Payne in 99 River Street (1953). He then signed a contract with 20th Century Fox for whom he made Untamed (1955), Violent Saturday (1955) for Director Richard Fleischer, House of Bamboo (1955), The Bottom of the Bottle (1956), and Between Heaven and Hell (1956) again with Fleischer.

Dexter was villainous to Joel McCrea in The Oklahoman (1957), produced by Walter Mirisch and could be seen in Run Silent Run Deep (1958), again as a villain. He largely focused on television though, appearing in episodes of Climax!, The Gale Storm Show, How to Marry a Millionaire, Pursuit, Studio One in Hollywood, Wagon Train, Have Gun - Will Travel, Zane Grey Theatre, Behind Closed Doors, Cimarron City, Yancy Derringer, This Man Dawson, 77 Sunset Strip, Colt 45, The Man from Blackhawk, Tightrope, Mr. Lucky, Bat Masterton, and Wanted: Dead or Alive.

He made the occasional feature film, such as Last Train from Gun Hill (1959), directed by John Sturges, and Vice Raid (1959), and was second billed in 13 Fighting Men (1960)

Dexter was then cast as a gunslinger in The Magnificent Seven (1960), directed by John Sturges, and made for Walter Mirisch, both of whom had worked with Dexter before. It became his best known role and most famous film. Characterizing him as a "tough guy at his best in The Magnificent Seven", Dexter's obituary in The Guardian singled out his portrayal of Harry Luck and claimed he was "overshadowed" by his contemporaries:

The film's success did not immediately benefit Dexter's career: he returned to television, guest starring in The Aquanauts, Hawaiian Eye, General Electric Theatre, Tales of Wells Fargo, Surfside 6, The Investigators, Death Valley Days and Alcoa Premiere. He could be seen in It Started in Tokyo (1961), The George Raft Story (1961) (playing Bugsy Siegel), X-15 (1962) with Charles Bronson and Johnny Cool (1963). Dexter supported Yul Brynner again in Taras Bulba (1962), Kings of the Sun (1963) (from the producers of Magnificent Seven), and Invitation to a Gunfighter (1964).

Dexter's friendship with Frank Sinatra began when Dexter saved Sinatra from drowning on May 10, 1964, during production of the World War II film, None but the Brave (1965), on the island of Kauai, Hawaii. Sinatra and Ruth Koch, the wife of Producer Howard Koch, were swimming at a beach when they were swept out to sea by the outgoing tide and nearly drowned. Sinatra's co-star Dexter and two surfers swam out and rescued them. Dexter was later awarded a Red Cross medal for his bravery.

After Dexter appeared in Bus Riley's Back in Town (1965), he made another with Sinatra, Von Ryan's Express (1965). He was a detective in Blindfold (1966). In 1965 Dexter revealed that acting made him "frustrated as hell. As an actor you don't have control over the medium you're in... you have no control over your destiny."

Dexter produced The Naked Runner (1967), which starred Sinatra and was filmed in London. The Director was Sidney J. Furie. Dexter and Furie clashed with Sinatra over the latter's unwillingness to finish the film, and, after it was completed, Dexter resigned. "I was the only guy who dropped Sinatra ... I couldn't put up with his nonsense", Dexter said at the time.

Publicly, Dexter denied any falling out with Sinatra. He claimed to have left Sinatra's company to make a film with Furie based on the Sam Sheppard case. The project eventually became The Lawyer (1970) starring Barry Newman as Petrocelli. Dexter also had guest roles on episodes of Mannix and Mission: Impossible. He produced two more films for Furie: Little Fauss and Big Halsy (1970) starring Robert Redford and Lady Sings the Blues (1972) starring Diana Ross as Billy Holiday.

He was married to Star-Kist tuna heiress Mary Bogdanovich from January 27, 1971 until her death on June 12, 1994. Later in 1994 he married June Deyer and remained with her until his death.

Dexter returned to acting with roles in Jory (1973), Shampoo (1975), Vigilante Force (1976), The Private Files of J. Edgar Hoover (1977), House Calls (1978) and Winter Kills (1979), and guest parts on McCloud, Kojak, S.W.A.T., Project U.F.O., and The Incredible Hulk. He was in the TV movies Law and Order (1976) and Valentine (1979).

Dexter produced the TV series Skag (1980) starring Karl Malden. His last role was in Cognac (1988).

Dexter died in Rancho Mirage, California, from emphysema, on December 11, 2002, at age 85, and is interred at Desert Memorial Park.