The five-time world medallist, who won combined gold in the 2019 worlds in Are, clocked one minute and 08.25 seconds.
Pinturault, whose family own a hotel in the French resort, was followed down the L'Eclipse piste by a trio of Austrians: defending world champion Marco Schwarz (at 0.06 seconds), Raphael Haaser (+0.14) and Vincent Kriechmayr (+0.58).
Loic Meillard will lead the charge for the Swiss team (+1.34) in the slalom scheduled for 1.30pm GMT, after world number one Marco Odermatt was disqualified after going wide on a gate.
"I've got the second run to enjoy myself," said Pinturault, who had been suffering from a cold and fever.
"The confidence is there. My last slaloms haven't been very good, perhaps that takes the pressure off me somewhat."
Norway's Aleksander Aamodt Kilde finished seventh, 1.05 seconds off the pace, but a right-hand injury sustained in Kitzbuhel last month means he will not compete in the slalom.
"This morning I woke up and wanted to fight for a medal but I tried slalom this morning and with my hand from Kitzbuhel it’s not really working in slalom just yet," Kilde said. "I tried a run, and no chance.
"I stretched some ligaments… it makes it unstable holding the pole and pushing out of the start, and boxing gates (in slalom), there’s no chance."
Pressure on 'Pintu'
Kilde hailed Pinturault as a "great skier" after his impressive super-G, but downplayed any real help skiing on home snow would give the Frenchman.
"When he hits the curves and gets to ski the way he does, he can win super-G as well," he said.
"Of course he know the terrain, he’s been training here for plenty of days, so that’s probably an advantage, but there’s also quite some pressure. You’re on home soil and everyone’s expecting a lot from him. I hope he gets a medal, he deserves it."
Kilde added: "I got a good run through. I didn’t risk anything more than I had to.
"But of course I know I’ve got to ski it more clean, give it another try in super-G in two days."
As one part of alpine skiing's golden couple, Kilde said his girlfriend, US star Mikaela Shiffrin, had been left disappointed after skiing out of the slalom of the women's combined when she looked certain to win gold
"The way she skis, brilliant," Kilde said.
"She's the fastest in the world in many disciplines right now. Yesterday for sure was a pity. I think she has mixed feelings going home from that race and not taking the gold when she was really close."
