The 18-year-old, the youngest slalom champion in Olympic history, led from the first run with a time of 52.99 seconds and held on to clock 1:50.66 minutes overall.
The American finished ahead of a trio of Swedish home favourites, with Maria Pietilae-Holmner finishing 0.6 behind Shiffrin in second.
Anna Swenn-Larsson rounded off the podium in a combined time of 1:52.16 while compatriot Frida Hansdotter claimed fourth place in 1:52.56.
Shiffrin now has an unassailable lead at the top of the standings having won four of the seven races so far and is on 438 points overall.
Hansdotter is in second place in the standings on 358 while Austrian Marlies Schild, who did not finish her second run, is third on 325 points.