The 39-year-old Movistar team rider and Tour favorite beat compatriot Demi Vollering by 3 minutes and 48 seconds in the eight-stage cycle race. Katarzyna “Kasia” Niewiadoma of Poland was third.
Van Vleuten, ranked No. 1 in the world, won stages seven and eight.
SD Worx’s Vollering secured the polka dot jersey for the Queen of the Mountains competition, while Trek-Segafredow’s Shirin Van Anrooij was the best of the young riders, securing the white jersey for 2022.
Canyon-SRAM Racing was the top team overall, beating FDJ-Suez-Futuroscope and Trek-Segafredo.
The race covered 1,029 kilometers (639 miles) in eastern France, finishing atop La Super Planche des Belles Filles.
It was the first women’s Tour de France since 1989.