Cantor was born as Edward Israel Iskovitz in New York City, the son of Russian Jewish immigrants. He was orphaned in childhood and made a living entertaining for coins on the city streets of Manhattan's Lower-East-Side.
In 1912 he appeared in Gus Edwards Review, and in 1916 debuted in the Ziegfeld Follies, where he would appear for years. For some time Cantor co-starred in an act with pioneer African-American comedian Bert Williams, both appearing in blackface; Cantor played William's son.
Cantor started making phonograph records in 1917, recording both comedy songs and routines and popular songs of the day, first for Victor, then for Aeoleon-Vocalion, Pathé, and Emerson. From 1921 through 1925 he had an exclusive contract with Columbia Records, then returned to Victor for the remainder of the decade.
Cantor was one of the era's most successful entertainers, but the 1929 Stock market crash suddenly took him from multi-millionaire status to being broke and deeply in debt. Cantor soon bounced back thanks to Hollywood movies and the radio. Cantor had appeared in a number of short films in the 1920s, but became a feature star in 1930 with the film Whoopee. He continued making feature films through 1948, the most notable including Roman Scandals, Ali Baba Goes to Town, and If You Knew Susie.
In the 1930s he also began hosting his own radio show, and by 1936 Cantor was the world's highest paid radio star. His radio shows began with a crowd chanting "We want Cantor - We want Cantor", said to have originated when a vaudeville audience used that chant to chase off an opening act who was on a bill before Cantor. Cantor's theme song was the 1903 pop tune "Ida, Sweet as Apple Cider", dedicated to Eddie's wife Ida.
He was a founder of the March of Dimes, and did much to publicize the battle against polio. Eddie Cantor served as first president of the Screen Actor's Guild.
Eddie Cantor's career declined somewhat in the late 1930s due to his public denunciations of Adolf Hitler and Fascism. Wishing to distance themselves from any political controversy, many sponsors dropped Cantor's shows. However Cantor's career bounced back with the United States entry into World War II.
Eddie Cantor wrote 8 books, including Caught Short (about the Crash of 1929) and his autobiography, My Life is in Your Hands.