De la Huerta was raised by her mother, along with her older sister Rafaela de la Paz (born November 5, 1981) in the New York City neighborhood of SoHo, located in Lower Manhattan. Her parents are Ricardo Ignacio de la Huerta y Ozores, the Spanish XVII Duke of Mandas and Villanueva (born November 17, 1944, in San Sebastián, Basque Country, Spain), and Judith Bruce (born October 23, 1946, in Minneapolis, Minnesota, United States). De la Huerta was born with recurrent cystic hygroma under her arm, which she has had treated with multiple surgeries. Her mother worked as an authority on birth control and women's issues in Third World countries. She attended private Saint Ann's School in the New York City borough of Brooklyn, with fellow student and Future fashion designer, Zac Posen, for whom she has since modeled. She also attended the performing arts camp Buck's Rock. De la Huerta spent summers with her father in Spain while attending high school.