The 18-year-old American pipped Tina Maze to the slalom crystal globe with a blistering performance on the final section of the second run.
Both women sobbed in the finish area - Shiffrin with joy and Maze with the frustration of finishing third and missing out on the slalom title to go with her overall, giant slalom and super-G cups.
Shiffrin had been 1.17 seconds behind Maze after the first leg but beat the best overall skier of the season by 0.35 seconds with her final combined time of one minute 55.60 seconds.
"It was another emotional day for me. I was so nervous, not only for me but also for Tina," said Shiffrin, who exchanged tweets of support with the Slovenian before the race.
"I'm not saying that I was hoping for her to win but I was so thrilled about everything she did this season that had I lost, it would still have been priceless to finish behind a skier like Tina," said Shiffrin after her fourth World Cup victory in the discipline this season.
Worn out after her exceptional season, Maze finished 0.15 behind runner-up Bernadette Schild of Austria, the sister of former world champion Marlies, who took the first podium of her career.
"This was not the way we had planned for this to finish," said Maze, who missed out on the downhill trophy by one point after Wednesday's final race was cancelled.
"I was expecting much more but I made a big mistake and there was no way to make up for it.
"I'm frustrated right now but once the dust settles I'll realise what I've done. You must be aware that Mikaela is much more of a slalom specialist than I am and that she deserved to win this cup. There's no way this is going to spoil my happiness."
Shiffrin finished the slalom season on 688 points, 33 more than Maze, who took her overall total to 2,314.
Maze will ski her 40th and final race of the season in Sunday's giant slalom on the same Lenzerheide course, hoping to end the winter on a last victory.
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- Tina Maze