The commanding victory in Hafjell was a record-extending 110th of the 31-year-old Olympic champion's World Cup career and a record ninth slalom win in 10 races this season.
Shiffrin moved 85 points clear of German rival Emma Aicher overall, with only 100 points remaining to be won from Wednesday's final giant slalom in the resort near 1994 Olympic venue Lillehammer.
The American had already clinched the slalom World Cup title for a record ninth time, and another Overall Globe would equal the women's record six that Austrian Annemarie Moser-Proell has held since the 1970s.
Shiffrin was fastest by 1.10 seconds in the first leg and finished 1.32 clear of Switzerland's Wendy Holdener, with Aicher completing the podium after moving up from fourth after the first run.
"I think this is just a symbol of the work that my team has been putting in and all the support I've had these years," said Shiffrin, after lifting the slalom Globe aloft at the finish area.
"Especially, the last three years to get back to the chance to be that high level and to win a globe.
"This season has been so exciting, quite like a whirlwind with all the wonderful races that we had and with the Olympics and with everything. It's been really pushing at a high level for a long time, and I'm grateful for it."
Shiffrin said she was ready for one last push against a 22-year-old rival she also considered a friend who had pushed her all the way.
The overall title is decided by points from all four disciplines - with Aicher an all-rounder, while Shiffrin does not do downhill and has competed in only a few of the super-Gs to gain whatever points she can.
The standings mean Shiffrin, whose last overall title was in 2023, will be sure of the biggest Crystal Globe if she finishes in the top 15 on Wednesday or Aicher fails to win.
"I'm so excited to watch what she does in the future," said the American. "For now, we have one more race to decide this one."