The American crossed the line in one minute 44.47 seconds in France, enough to give her top place on the podium, ahead of Viktoria Rebensburg and Elisabeth Goergl (both +0.19secs).
Tina Maze, who won the first downhill race of the season, had to settle for seventh place after finishing 0.48secs back, with three Swiss racers - Lara Gut (+0.39secs), Dominique Gisin (+0.46secs) and Fabienne Suter (+0.46secs) - ahead of her.
It is Vonn's second victory in the discipline this season after she triumphed in Lake Louise earlier this month, and shows she has fully recovered after a year out following two knee operations and a fractured shin.
A slow start to her run saw the 30-year-old third at the end of the first sector, but she quickly found her rhythm over the 2,842metre course, and stopped the clock with a comfortable advantage over her rivals.
Defending overall champion Anna Fenninger continues to search for her first win since the opening event of the season in Solden, the Austrian having to settle for 11th place on this occasion.
Victory moves Vonn to the top of the downhill rankings with 232 points, with Maze 64 points back after only collecting 36 at the French resort.
The Slovenian remains in the lead in the overall standings, though, with Fenninger holding on to second place, and Vonn moving into third ahead of Kathrin Zettel.