The daughter of a psychologist and a college professor, Thurman was raised in Amherst, Massachusetts and Woodstock, New York. She attended a preparatory school in New England, where at fifteen she was discovered by two New York agents. At sixteen she transferred to a Professional Children's School in New York City in order to pursue an acting career.

Thurman's entrance onto the mainstream film scene began with Johnny Be Good, opposite Anthony Michael Hall. But it was her role as the goddess Venus in Terry Gilliam's 1988 fantasy The Adventures Of Baron Munchausen which brought her international acclaim. This striking and versatile actress went on to receive critical acclaim for her portrayal of a virginal 18th Century convent girl, Cecile de Volanges, seduced by John Malkovich in Stephen Frears' Dangerous Liaisons. The following year she starred opposite Fred Ward and Maria de Medeiros in Philip Kaufman's Henry And June playing the neurotic and erotic bisexual spouse of Henry Miller. She then played Daphne McBain; one of a trio of Dabney Coleman's spoiled children in the comedy Where The Heart Is, directed by John Boorman.