The 39-year-old Movistar Team rider and Tour favorite bested compatriot Demi Vollering by 3 minutes and 48 seconds in the eight-stage bike race. Katarzyna “Kasia” Niewiadoma of Poland finished third.
Van Vleuten, ranked No. 1 in the world, won stages seven and eight.
Vollering, of Team SD Worx, secured the polka dot jersey for the Queen of the Mountains competition, while Shirin van Anrooij, of Trek-Segafredowas best of the young riders, securing the white jersey for 2022.
Canyon-SRAM Racing was the top team overall, beating out 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.
This was the first Women’s Tour de France since 1989.