Switzerland's Wendy Holdener, who won gold in the last week's alpine combined event, was in second, at 0.38sec.
If she continues to hold the lead through the rest of the season, Shiffrin would become only the third US female racer to win the overall World Cup title.
Slovak pair Veronika Velez Zuzulova (+0.59) and Petra Vlhova (+0.76) were next, ahead of Sweden's Frida Hansdotter, Switzerland's Michelle Gisin and Austrian Michaela Kirchgasser.
"Tessa deserves winning this, she's done so well all season", Shiffrin said, according to the International Ski Federation.
Shiffrin is her generation's dominant slalom skier, with 24 of her 28 World Cup wins coming in that tech discipline.
Mikaela Shiffrin was in a world of her own on Saturday, extending her unbeaten record in slalom gold medal events.
"When I saw 1.6, it was like, 'Is the time wrong?' " Shiffrin said.
She was unstoppable on the second run and crossed the line in a time of 1 min 37.27secs.
"Three [gold] medals is great, but today is really special today for me because I finally skied this the way I wanted to, and that's what means a lot to me today".
Worley, born to an Australian father and French mother, joins an elite band of racers to have won two giant slalom golds - only Anja Paerson, Deborah Compagnoni, Mariele Goitschel and Vreni Schneider having previously achieved the feat.
She has won the slalom at every major event since she was 17 - world championships in 2013, 2015 and 2017, plus the Olympics in 2014. "That run felt really good!" she said afterward about her climatic second run, in itself 0.85 seconds faster than Sarka Strachova's next-best second run time for the Czech Republic.
She now stands alongside Emile Allias (four) and behind just Goitschel (seven) and Jean-Claude Killy (six) in the pantheon of French skiers with most world titles.
The World Alpine Skiing Championships are set to draw to a close tomorrow with the 11 medal event, the men's slalom. "Whenever I am at (ski) world championships, she is winning".
"I knew just a small mistake like this could be fatal and I just told myself to push harder and it was enough".
It was actually really good for the second run.