The Frenchman's decision to skip the speed events at Val Gardena paid dividends as he finally clinched the giant slalom classic at Alta Badia.
The 29-year-old had been on the podium twice before, both times looking up at Marcel Hirscher who won the race six times in succession from 2013 to 2018.
He won by just seven-hundredths of a second from 20-year-old Norwegian Atle Lie McGrath who had the best result of his promising career.
Switzerland's Justin Murisier (+0.24s) had a excellent run to move up from 11th place to third and join McGrath in achieving a first World Cup podium finish.
Pinturault said afterwards, "It was a huge fight. I think the light was slowly going down because it started to be a little bit late and it makes such a different on the course. But I tried my best and I pushed really hard and it paid off.
"It's a special day because the Gran Risa is always a 'myth' and I'm really happy that I could win it today." - Alexis Pinturault to FIS
Marco Odermatt was fourth ahead of the United States' Tommy Ford who has now finished in the top six in his last three races.
That was not enough to see him retain his overall World Cup lead as Pinturault took over at the top by just one point, 376 to 375, with Odermatt third on 340.
Several skiers struggled on the second run with icy conditions making the turns at the top of the course particularly demanding.
Norway's reigning giant slalom world champion Henrik Kristoffersen had a day to forget, finishing down in 15th.
Triple Olympic Winter Games gold medallist River Radamus told Olympic Channel that he was hoping for a good showing on his favourite course, and he was 20th to notch up his third career top-20 finish.
Double Olympic gold medallist Ted Ligety toiled on his second run and finished 26th.
Pinturault will hope to extend his lead in Monday's slalom at Alta Badia.