Shiffrin trailed Vlhova by 0.07 seconds after the first leg in Austria but the US star wiped out the deficit to collect her sixth victory of the season.
She finished 0.27sec clear of Vlhova, winning for the fourth time in seven slaloms and making amends for straddling a gate in Kranjska Gora earlier this month.
"I'm really proud of this evening and very thankful for my whole team," said Shiffrin, wiping away tears.
She skipped last weekend's speed events in Austria to recover from a cold. She then went to visit boyfriend Aleksander Aamodt Kilde in a Swiss hospital after his season-ending crash in the Wengen downhill.
Norwegian Kilde underwent surgery in nearby Bern after suffering a dislocated shoulder and a cut to his calf.
"These last days have been very challenging. They've been so supportive and helped me go see Aleks," said Shiffrin.
Sweden's Sara Hector, the Olympic giant slalom champion, took third place at 1.11sec. All 14 of her previous World Cup podiums had come in the giant slalom.
Vlhova, winner of the three other slaloms this term, moved up to second in the overall standings behind Shiffrin, trailing the five-time World Cup champion by 227 points.
The next stop on the women's circuit is in Jasna, Slovakia, which still stage a giant slalom and slalom this weekend.
