Martin was born on June 7, 1917, in Steubenville, Ohio, to an Italian father, Gaetano Alfonso Crocetti (1894-1967), and an Italian-American mother, Angela Crocetti (nee Barra; 1899-1966). They were married in 1914. His father, who was a barber, was originally from Montesilvano, in Abruzzo, and his maternal grandparents' origins are believed to be also from Abruzzo, although they are not clearly known.

Martin attracted the attention of Metro-Goldwyn-Mayer and Columbia Pictures, but a Hollywood contract was not forthcoming. He met comic Jerry Lewis at the Glass Hat Club in New York, where both were performing. Martin and Lewis formed a fast friendship which led to their participation in each other's acts and the formation of a music-comedy team. Martin and Lewis's debut together occurred at Atlantic City's 500 Club on July 24, 1946, and they were not well received. The owner, Skinny D'Amato, warned them that if they did not come up with a better act for their second show that night, they would be fired. Huddling in the alley behind the club, Lewis and Martin agreed to "go for broke", they divided their act between songs, skits, and ad-libbed material. Martin sang and Lewis dressed as a busboy, dropping plates and making a shambles of Martin's performance and the club's decorum until Lewis was chased from the room as Martin pelted him with breadrolls.  They did slapstick, reeled off old vaudeville jokes, and did whatever else popped into their heads. The audience laughed. This success led to a series of well-paying engagements on the Eastern seaboard, culminating in a run at New York's Copacabana. The act consisted of Lewis interrupting and heckling Martin while he was trying to sing, with the two ultimately chasing each other around the stage. The secret, both said, is that they ignored the audience and played to each other. The team made its TV debut on the first broadcast of CBS-TV network's The Ed Sullivan Show (then called "The Toast Of The Town) on June 20, 1948, with composers Rodgers and Hammerstein also appearing. Hoping to improve their act, the two hired young comedy writers Norman Lear and Ed Simmons to write their bits. With the assistance of both Lear and Simmons, the two would take their act beyond nightclubs.  A radio series began in 1949, the year Martin and Lewis signed with Paramount producer Hal B. Wallis as comedy relief for the movie My Friend Irma. Their agent, Abby Greshler, negotiated one of Hollywood's best deals: although they received only $75,000 between them for their films with Wallis, Martin and Lewis were free to do one outside film a year, which they would co-produce through their own York Productions.  They also controlled their club, record, radio, and television appearances, and through these they earned millions of dollars. In Dean & Me, Lewis calls Martin one of the great comic geniuses of all time. They were friends, as well, with Lewis acting as best man when Martin remarried in 1949. But harsh comments from critics, as well as frustration with the similarity of Martin and Lewis movies, which producer Hal Wallis refused to change, led to Martin's dissatisfaction. He put less enthusiasm into the work, leading to escalating arguments with Lewis. Martin told his partner he was "nothing to me but a dollar sign". The act broke up in 1956, 10 years to the day from the first teaming.

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