It was only the fourth win in the discipline for the American who finished 0.15 seconds ahead of the Italian Sofia Goggia, who was imperious in the super-G on Friday, and 0.17sec clear of Federica Brignone, another Italian.
Shiffrin wearing number 3 on her bib, skied with great precision, cleverly negotiating a long section that was more favourable to speed specialists, before mastering a more technical intermediate section.
The five-time holder of the crystal globe and world number one for the last two seasons, is now 195 points ahead of Brignone in the overall standings, and 215 clear of Switzerland's Lara Gut-Behrami who could only finish 13th, 0.89sec behind Shiffrin.
The Slovakian Petra Vlhova, a technical skier who has given St-Moritz a miss, has dropped to fourth place, 229 points behind her rival.
Action in St Moritz concludes with a second super-G on Sunday.
