Vonn finished with a time of 1 minute, 37.70 seconds, 0.42 seconds ahead of Germany's Maria Riesch.
The victory was Vonn's eighth of the season, which includes five downhills and Friday's super G.
"It's a phenomenal achievement," said U.S. Women's Head Coach Jim Tracy. "It's something that, when you start your career, you dream and you wonder if you can ever get to be that good. All of us are extremely proud of her."
Anja Pearson of Sweden and Nadia Kamer of Switzerland tied for third.
The U.S. Olympic ski team will be announced Sunday after the giant slalom.