Uma Thurman was given a Buddhist upbringing. Her half-Swedish, half-German mother, Nena von Schlebrugg, was briefly married to Timothy Leary (to whom she was introduced by Salvador Dalí) before marrying Uma's father, Robert Thurman, a professor of Indo-Tibetan Buddhist studies of British ancestry. She is named after a Hindu goddess. She has three brothers, named Ganden, Dechen and Mipam. For a long time, she was a spokesmodel for cosmetics company Lancôme. As of 2005, she is a spokesmodel for luxurious French fashion house Louis Vuitton.

She left her high school, Northfield Mount Hermon, at the age of 15 to pursue an acting career in New York City. In 1990 she married actor Gary Oldman but divorced him two years later. On May 1, 1998, she married actor Ethan Hawke, whom she had met at the set of Gattaca. Hawke's book For Karuna was dedicated to her. They had two children, a daughter Maya Ray and a son Levon Roan. In 2003, Thurman and Hawke split, and in 2004, the couple filed for divorce. She now resides in Hyde Park, New York.