The 23-year-old – daughter of 1992 Olympic downhill champion Patrick Ortlieb – secured her first podium finish a week earlier in Crans Montana, Switzerland, but bettered that performance by squeezing past the home favourite by one-hundredth of a second to win.
Completing the top three was Swiss star Corinne Suter, who lost control of her right pole halfway through her run and finished 0.07s behind.
Ortlieb snatches memorable first World Cup win
With only the season-ending race in Cortina d'Ampezzo, Italy, remaining in the Super-G discipline, Suter sits 19 points ahead of Brignone, who leads the overall World Cup standings by 153 points.
But Saturday's result belonged to Ortlieb, who couldn't hide her delight at the end of the finest run of her career to date.
"This is a dream, of course," she said. "This is what I work for every day.
"My summer training went well and I finished fourth in the first downhill this season which gave me a lot of confidence and I'm just so delighted."