Duke was the only child of tobacco and electric energy tycoon James Buchanan Duke and his second wife, Nanaline Holt Inman, widow of Dr. William Patterson Inman. At his death in 1925, the elder Duke's will bequeathed the majority of his estate to his wife and daughter, along with $17,000,000, in two separate clauses of the will, to The Duke Endowment he had created in 1924. The total value of the estate was not disclosed, but was estimated variously at $60,000,000 and $100,000,000.
She was presented to society as a debutante in 1930, aged 18, at a ball at Rough Point, the family residence in Newport, Rhode Island. She received large bequests from her father's will when she turned 21, 25, and 30; she was sometimes referred to as the "world's richest girl". Her mother died in 1962, leaving her jewelry and a coat.
When Duke came of age, she used her wealth to pursue a variety of interests, including extensive world travel and the arts. During World War II, she worked in a canteen for sailors in Egypt, taking a salary of one dollar a year. In 1945, Duke began a short-lived career as a foreign correspondent for the International News Service, reporting from different cities across the war-ravaged Europe. After the war, she moved to Paris and wrote for the magazine Harper's Bazaar.
While living in Hawaii, Duke became the first woman to take up competition surfing under the tutelage of surfing champion and Olympic swimmer Duke Kahanamoku and his brothers. A lover of animals, in particular her dogs and pet camels, in her later years Duke became a wildlife refuge supporter, an environmental conservationist, and a patron of historic preservation.
Duke acquired a number of homes. Her principal residence and official domicile was Duke Farms, her father's 2,700 acre estate in Hillsborough Township, New Jersey. Here she created Duke Gardens, 60,000-square-foot public indoor botanical display that were among the largest in America.
Duke married twice, the first time in 1935 to James H. R. Cromwell, the son of Palm Beach society doyenne Eva Stotesbury. Cromwell, a New Deal advocate, used his wife's fortune to enter the political arena, becoming U.S. Ambassador to Canada in 1940. The couple had a daughter, Arden, who lived for only one day. They divorced in 1943.
On September 1, 1947, while in Paris, Duke became the third wife of Porfirio Rubirosa, a diplomat from the Dominican Republic. She reportedly paid his wife, Danielle Darrieux, $1 million to agree to an uncontested divorce. Because of her great wealth, Duke's marriage to Rubirosa attracted the attention of the U.S. State Department, which cautioned her against using her money to promote political agendas. Further, there was concern that in case of her death, a foreign government could gain too much leverage. Thus Rubirosa had to sign a pre-nuptial agreement; during the marriage, though, she gave Rubirosa several million dollars in gifts, including a stable of polo ponies, sports cars, a converted B-25 bomber, and, in the divorce settlement, a 17th-century house in Paris. While she subsequently had a number of relationships, Duke never remarried. One of Doris Duke´s best friends was the Brazilian Aimee de Heeren, who tried to cheer her up whenever a marriage was over.
In 1992, at the age of 79, Duke had a facelift. She began trying to walk while she was still heavily medicated and fell, breaking her hip. In January 1993, she underwent surgery for a knee replacement. She was hospitalized from February 2 to April 15. She underwent a second knee surgery in July of that year. A day after returning home from this second surgery, she suffered a severe stroke. Doris Duke died at her Falcon's Lair home on October 28, 1993, at the age of 80. The cause was progressive pulmonary edema resulting in cardiac arrest, according to a spokesman for Bernard Lafferty, the executor named by Duke's last will, who was with her at her death.