Vonn posted her 49th career World Cup win with a time of 1 minute, 43.65 seconds, a whopping 1.42 seconds ahead of Maria Hoefl-Riesch of Germany.
Tina Weirather of Liechtenstein placed third followed by Slovenia's Tina Maze, who was in second place in the overall points standings behind front-runner Vonn.
"I've struggled in St. Moritz in the past and for some reason have always made major mistakes and have never won a downhill here," said Vonn. "Today I just tried to stay really relaxed. I knew where I had to execute the line and I think I did that."
Vonn won the super-combined at St. Moritz Friday and sets her sights on another super-combined victory Sunday, which will includes the super-G and slalom courses.