The Spanish award's jury said that Hustvedt's "ambitious" work "delves into aspects that depict a convulsed and disconcerting present from a feminist perspective."
Born in Minnesota, Hustvedt has written dozens of novels, essays and poems influenced by neurosciences, psychoanalysis and the arts. Her books have been translated to more than 30 languages.
Hustvedt is married to writer Paul Auster, who won the same prize in 2006.
The 50,000-euro ($55,000) award is one of eight annual prizes, named after Crown Princess Leonor, handed out to honour people in fields including sports, sciences and arts.
Last year's literature award went to French writer Fred Vargas.
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