Martin began his show business career at age seventeen, singing in Ohio nightclubs near his hometown. During a stint with the Ernie McKay band, he was noticed by Cleveland bandleader Sammy Watkins, who hired him as the bands featured vocalist. He began touring with Watkins in 1938, and in 1940, changed his name to Dean Martin. In September 1943, Martin signed an exclusive contract with MCA to sing at the Riobamba Room in New York, and in 1944 he was given his own fifteen-minute radio program broadcasting from New York City, Songs by Dean Martin. In 1946 he signed a contract and recorded four songs with Diamond Records.

During a club engagement in 1946, Martin met Jerry Lewis and the two began joking around with each other during their respective acts. They teamed up in 1947, with Martin playing the straight man to Lewis's clown. NBC broadcast a regular thirty-minute radio program featuring the pair in 1949, and they made their television debut in the Colgate Comedy Hour in 1950. The immensely popular Martin and Lewis team made sixteen films together between 1949 and 1956.

They last performed together at the Copacabana in New York, on July 24, 1956. After ten years as a team, they split up due to creative differences. Martin struck out on his own and resumed his singing career, recording such hit records for Capitol as "That's Amore," "Memories are Made of This," "When You're Smiling," and "Oh Marie." He also resumed acting in films, and in 1958, Martin received critical acclaim after appearing with Montgomery Clift and Marlon Brando in "The Young Lions."

It was around this time that Martin began performing in Las Vegas with a group of close friends who were members of a Hollywood clique known as "The Rat Pack." The group, which included Martin, Frank Sinatra, Sammy Davis, Jr., Joey Bishop, and Martin appeared in a total of fifty-one films in his lifetime, including “Some Came Running” (1958) with Shirley MacLaine and Frank Sinatra, “Bells Are Ringing” (1960) with Judy Holliday, “Rio Bravo” (1959) with John Wayne, “Toys in the Attic” (1963), “Airport” (1970), “Cannonball Run” (1981) and “Cannonball Run II” (1984).

In 1962, Martin left Capitol Records and signed with Reprise. In 1964, he recorded his blockbuster hit, "Everybody Loves Somebody," which beat the Beatles to become the No. 1 hit in America for one week. It became the theme song for his television variety series, “The Dean Martin Show”, which ran on NBC for eight years starting in 1965. Martin followed this with “The Dean Martin Comedy Hour”, which ran from 1973 to 1974. An indelible part of Martin's television "schtick" was his comedic portrayal of life as an alcoholic lush, which many people never realized was just an act.

Martin was married three times, first to wife Elizabeth Anne McDonald on October 2, 1941. The couple had four children: Stephen (Craig), born June 29, 1942; Claudia, born March 16, 1944; Barbara (Gail), born April 11, 1945; and Deana (Dina), born August 19, 1948. He married second wife Jeanne Biegger on September 1, 1949 and had three children: Dino Paul Jr., born November 17, 1951; Ricci James, born September 20, 1953; and Gina Caroline, born December 20, 1956. In 1973, Martin married third wife Catherine Mae Hawn, and adopted a daughter Sasha. Their marriage ended in 1976.

Martin suffered a tragic loss when his son, Dino Jr., was killed in a plane crash during a military training exercise in 1987. He retired from show business after a 1988-89 concert tour with fellow rat-packers Sammy Davis, Jr. and Frank Sinatra, which ended for Martin after he decided to depart the tour and was replaced by Liza Minelli for the remainder of the tour. Martin died of acute respiratory failure in Beverly Hills on December 25, 1995.