Shiffrin won the slalom, finishing 0.61 seconds ahead of second-placed Croatian Zrinka Ljutic, to become the first skier, male or female, to reach triple digits in World Cup race victories.
American Paula Moltzan finished third, while world champion Camille Rast crashed out in her first run.
Shiffrin's hunt for her 100th career World Cup win was put on hold after she crashed during a giant slalom race in Killington, Vermont, in November and suffered a puncture wound in her abdomen.
She returned to racing at the end of January and won a record-equalling 15th career world championships medal earlier this month in Saalbach when she and downhill champion Breezy Johnson struck gold in the new women's team combined event.
Shiffrin had appeared slightly off the pace in her World Cup return, finishing 25th in the Sestriere giant slalom on Friday and failing to make the cut in the same category on Saturday.
In January 2023, Shiffrin passed compatriot Lindsey Vonn by winning her 83rd World Cup race, the most by a female skier.
Less than two months later the twice Olympic gold medallist established herself as the most successful Alpine skier in World Cup history, male or female, when she topped retired Swedish great Ingemar Stenmark's decades-old record of 86 victories.
The women's World Cup returns in Kvitfjell, Norway, on February 28th.
In the men's World Cup super-G in Crans-Montana, Switzerland, on Saturday, overall World Cup leader and home hero Marco Odermatt took his 45th World Cup victory ahead of compatriot Alexis Monney, while Italian veteran Dominik Paris completed the podium.