Vaucluse is a department in the southeastern French region of Provence-Alpes-Côte d'Azur. It had a population of 559,016 as of 2016. The department's prefecture is Avignon.

It is named after a spring, the Fontaine de Vaucluse, one of the largest karst springs in the world. The name Vaucluse itself derives from the Latin Vallis Clausa ("closed valley") as the valley ends in a cliff face from which the spring emanates.

Vaucluse was created on 12 August 1793 out of parts of the departments of Bouches-du-Rhône, Drôme and Basses-Alpes, later renamed Alpes-de-Haute-Provence. The then rural department was, like the nearby city of Lyon, a hotbed of the French Resistance in World War II.

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