The veteran van Vleuten rode a controlled ride and decided the Tour during the final climb on the mountain stage between Lure and La Planche des Belles Filles in the Vosges mountain range.
Demi Vollering of the Netherlands was second, both in the stage and overall, and Poland's Katarzyna Niewiadoma finished third overall after a fourth place in the final stage.
Among cyclists under the age of 23, Swede Julia Borgström, 21, finished third overall.
Shirin van Anrooij, 20, from the Netherlands won the youth competition.