During his conflict with Ziegfeld Cantor worked for the rival producers the Shubert brothers. He was a great success in their productions of Broadway Brevities (1920), She Don't Wanna (1921), and Make It Snappy (1922). Finally Ziegfeld and Cantor resolved their conflict and Cantor returned to star in Kid Boots (1923), directed by Ziegfeld on Broadway. In this show Cantor played a clever caddie at a golf resort who sold golf lessons and, on the side, bootleg whiskey. This was his first full-length part on Broadway, and it proved to audiences and producers alike that his act could carry an entire show. In 1927 he was a smashing success in his return to Ziegfeld's Follies, and in the following year he starred in another Ziegfeld musical comedy, Whoopee. In Whoopee Cantor played the part of Henry Williams, a chronic hypochondriac travelling to a dude ranch. He sang "Makin' Whoopee," one of his all time favorite songs, and the success of this show led Eddie Cantor to film stardom.

Cantor had made his first film in 1911 in a test talking picture. In Widow at the Races he starred with his friend George Jessel and was directed by none other than Thomas Edison. He started working seriously in film in 1926 (Kid Boots), but it was Whoopee (1930) which made him a film star. Among his best films were Palmy Days (1931), Kid from Spain (1932), Roman Scandals (1933), and Kid Millions (1934).

In 1931 Cantor had returned to the stage at the Palace (an old vaudeville house) and headed the bill with George Jessel. The show, which also starred the famous comedy team of Burns and Allen, was so popular that it was held over for six weeks. His next stage role was in Banjo Eyes (which became his nickname) in 1942.

Cantor frequently appeared on stage in blackface with a straw hat, wire-rimmed glasses, white gloves, black tie, and tight checked trousers. He had large popping eyes and used fast, mincing steps, jumping-jack antics, and hand clapping. He was known for his Jewish humor, for which he employed a Yiddish accent. In one sketch he announced, "I'd go to war for my mother country, Russia—darkest Russia—for all my relatives there, General Walkowitch, Hzkowitch, Eczema" When he was questioned about Eczema he answered, "Yes, that's another itch."

In addition to his stage and film career Cantor was host of the Chase and Sanborne Hour (1931), a popular radio show, and of the Eddie Cantor Show (1935-1939). He also made many recordings and wrote several books. He was coauthor of Silks and Satins and author of such humorous books as Earl Carroll's Sketch Book, Your Next President, Caught Short: A Saga of Wailing Wall Street, Between the Acts, Who's Hooey, and World's Book of Best Jokes. With David Freedman he paid tribute to his mentor in Ziegfeld, the Great Glorifier. Cantor wrote two autobiographies, My Life Is in Your Hands (1928) and Take My Life (1930). He was also host of the television show The Colgate Comedy Hour. His life was recorded on film in 1953 in The Eddie Cantor Story, and in 1956 he was awarded a special Oscar for distinguished service to the motion picture industry.

Cantor was admired as a tireless, conscientious humanitarian. His outspoken criticism of what he called fascist government officials resulted in his being blacklisted for a year (1931). Nevertheless, always appreciated for his modesty, kindness, and generosity, he was granted, in 1951, an honorary Doctorate of Humane Letters by Temple University.

He was dedicated to many charities. Among his favorites were a summer camp for poor children, the March of Dimes (which he helped to create), and various Jewish causes. In 1962 the State of Israel gave him the Medallion of Valor for his extraordinary efforts on behalf of that nation.

He was a devoted family man who married his childhood sweetheart, Ida Tobias. They had five daughters. Cantor died October 10, 1964, at the age of 72.