The American won by 0.78s from France's Tessa Worley, with Manuela Moelgg finished a further 0.31s behind, as Switzerland's Lara Gut could only manage fourth.
The win moved Shiffrin up to second in the giant slalom standings, 55 points behind Worley, and above Gut to the top of the overall leaderboard.
Mikaela Shiffrin surges to historic treble in Semmering
The Semmering event only happened due to the terminated race in Courchevel, a week ago, that was abandoned because of excessive wind after the race began. Shiffrin laid down the fastest time in the first run, being the only racer to drop below the minute mark.
AlpSki: 1st leg GS - Shiffrin
Image credit: Eurosport
Her second run was only good enough for sixth, but she had already built up enough of a lead to take the convincing win.
"It was so much fun, and I felt relaxed and really clean. It was nice to ski that," Shiffrin said between runs.
"I came into this race thinking gosh, I have to be excited to race – not dread it and have to come up with a plan. Just go and see what happens, and it felt good."
Shiffrin is now 55 points ahead of Gut in the overall standings, but with another giant slalom and slalom scheduled in Semmering over the next two days, the standings could well look different by the time the racers leave Austria at the end of the week.
Video: Shiffrin negotiates treacherous conditions on second run
Dominant Mikaela Shiffrin wins Giant Slalom in Semmering
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