Victory in Finnish Lapland also gave the American her 139th podium place. Sweden's Ingemar Stenmark holds the record for the most podiums with 155 in the men's events.
Vlhova had a lead of nearly one second after the first run and continued to extend her advantage at the top of the second run until she straddled a gate halfway down the course and failed to finish.
Shiffrin clocked one minute 51.68 seconds, 0.18 seconds ahead of Leona Popovic from Croatia. Germany's Lena Duerr ended third, 0.30 seconds behind Shiffrin.
"I was sort of settled on second place," Shiffrin said.
"Petra really did a masterclass in slalom skiing this weekend - in my mind, she earned this victory and I'm quite lucky to have it."
The men's downhill race in Zermatt-Cervinia, on the border between Switzerland and Italy, was called off earlier on Sunday, for the second day in a row, due to heavy snowfall and winds.
