The 29-year-old American has Olympic and world championship gold medals in the combined event but had never before won on the World Cup circuit.
Ligety overturned a 1.22-second deficit from the slalom to beat Pinturault by 0.22. Natko Zrncic-Dim of Croatia was third, trailing 1.08 behind Ligety's combined time of 2 minutes, 44.74 seconds.
Aksel Lund Svindal of Norway was fifth, enough to take the overall World Cup lead from Austrian rival Marcel Hirscher, who skips speed events.
Bode Miller, the super-combined Olympic champion, was ninth after finishing seventh in a tricky slalom in the morning.
Ligety's 20th career World Cup win was his first outside his specialist giant slalom discipline. But he won the world title in super-combined last year and earned the gold medal at the 2006 Turin Olympics when traditional combined included two slalom legs.
Ligety also extended his advantage over Pinturault in the race for third place in the overall standings.
Svindal got 45 World Cup points Friday to lead Hirscher by 22, and is favoured to pad his lead Saturday in the classic Lauberhorn downhill. Hirscher is expected to score heavily in the slalom on Saunday, which Svindal will skip.
Ligety trails Svindal by 264 points.
Organizers ran the slalom first on Friday to give time for cloud cover to clear and also to prepare a shortened, 3.1-kilometre (1.9-mile) downhill course after heavy overnight snowfall.