He often referred to his nose as the schnozzola (Italianization of the American Yiddish slang word schnoz, meaning big nose) and that became his nickname.
Durante dropped out of school in seventh grade to become a full-time ragtime pianist. He first played with his cousin, whose name was also Jimmy Durante. It was a family act, but he was too professional for his cousin. He continued working the city's piano bar circuit and earned the nickname "Ragtime Jimmy" before he joined the Original New Orleans Jazz Band, a well known band in New York City. In 1920 the group was renamed Jimmy Durante's Jazz Band.
By the mid-1920s, Durante had become a vaudeville star and radio personality. By 1934, Durante had a major record hit with his own novelty composition, Inka Dinka Doo and the song became his theme song for the rest of his life.
In 1935, Durante starred on Broadway in the stage musical Jumbo. During the early 1930s, Durante alternated between Hollywood, starring in motion pictures and Broadway.
On September 10, 1933, Durante appeared on Eddie Cantor's radio show, The Chase and Sanborn Hour, continuing until November 12 of that year. When Cantor left the show, Durante took over for about five months before moving on to The Jumbo Fire Chief Program (1935–1936). Durante teamed with Garry Moore for The Durante-Moore Show in 1943. Moore left in mid-1947, and the program returned in the Fall as The Jimmy Durante Show and it lasted three more years.
Although Durante made his television debut on November 1, 1950 he continued to keep a presence in radio. From 1950 to 1951, Durante was the host once a month (alternating with Ed Wynn, Danny Thomas and Jack Carson) on a comedy-variety series Four Star Revue. Jimmy continued with the show until 1954. Durante then had a half-hour variety show (The Jimmy Durante Show) on television from October 1954 to June 1956.
Beginning in the early 1950s, Durante was often was seen regularly in Las Vegas after Sunday Mass outside of the Guardian Angel Cathedral standing next to the priest and greeting the people as they left Mass.
Several times in the 1960s, Durante served as host of Hollywood Palace variety show. His last regular television appearance was co-starring with the Lennon Sisters on Jimmy Durante Presents the Lennon Sisters Hour, which lasted for one season (1969–1970).
Durante's first wife was Jean Olson, whom he married in June of 1921. She was born in Ohio and was 46 years old when she died on Valentine's Day in 1943, after a lingering heart ailment of about two years. At the time Durante was touring in New York and returned home immediately to complete the funeral arrangements.
Besides his song Inka Dinka Doo, Durante's shows had the trademark signoff, "Good night, Mrs. Calabash, wherever you are." For years no one knew who Mrs. Calabash referred to and Durante preferred to keep the mystery alive until 1966.
One theory was that it referred to the owner of a restaurant in Calabash, North Carolina, where Durante and his troupe had stopped to eat. He was so taken by the food, the service, and the chitchat he told the owner that he would make her famous. Since he did not know her name, he referred to her as Mrs. Calabash.
At a National Press Club meeting in 1966, Durante finally revealed that it was a tribute to his wife. While driving across the country, they stopped in a small town called Calabash, North Carolina whose name Jean had loved. Mrs. Calabash became his pet name for her, and he eventually adopted it as his signature sign off.
Durante married his second wife, Margie Little, at St. Malachy Roman Catholic Church in New York City on December 14, 1960. As a teenager she had been Queen of the New Jersey State Fair. She attended New York University before being hired by the legendary Copacabana in New York City. She and Durante met there 16 years before their marriage, when he performed there and she was a hatcheck girl. She was 41 and he 67 when they married.
With help from their attorney, the couple adopted a baby, Cecilia Alicia (nicknamed CeCe and now known as CeCe Durante-Bloum), on Christmas Day, 1961. She became a champion horsewoman and then a horse trainer and horseriding instructor. She died on June 7, 2009, at the age of 89.
On August 15, 1958, for his charitable acts, Durante was awarded a loving cup by the Al Bahr Shriners Temple. Also, Durante had started out his career in the 1920s teamed with Lou Clayton and Eddie Jackson who remained his his closest friends and they were kept on his payroll for the rest of their lives.
Durante's love for children continued through the Fraternal Order of Eagles, who among many causes raise money for handicapped and abused children. At Durante's first appearance at the Eagles International Convention in 1961, when asked about his fee for performing, Durante replied, "Do not even mention money judge or I'll have to mention a figure that'll make ya sorry ya brought it up." "What can we do then?" asked Hansen. "Help da kids," was Durante's reply. Durante performed for many years at Eagles conventions free of charge, even refusing travel money. The Fraternal Order of Eagles changed the name of their children's fund to the Jimmy Durante Children's Fund in his honor, and in his memory have raised over 20 million dollars to help children.
Durante was an active member of the Democratic Party. In 1933, he appeared in an advertisement shown in theaters supporting Franklin D. Roosevelt's New Deal programs and wrote a musical score titled Give a Man a Job to accompany it. He performed at both the inaugural gala for President John F. Kennedy in 1961 and a year later at the famous Madison Square Garden rally for the Democratic party that featured Marilyn Monroe singing "Happy Birthday" to JFK.
Durante continued his film appearances through the early 1970s and retired from performing in 1972 after he became wheelchair-bound following a stroke. He died of pneumonia in Santa Monica, California on January 29, 1980, 12 days before he would have turned 87. He is interred at Holy Cross Cemetery in Culver City, California.