Austria's Matthias Mayer got his first win on the downhill in Bormio, edging out compatriot Vincent Kriechmayr by 0.04 seconds to take his 10th World Cup victory.
Switzerland's Urs Kryenbuhl finished third.
Double Olympic champion Mayer had finished second behind Dominik Paris twice previously - but the Italian, currently still recovering from a knee ligament injury, was off the pace on the Stelvio, finishing fourth.
The USA's Ryan Cochran-Siegle, who won Tuesday's Super-G, had been quickest in the training runs, but lost his balance late on and finished in seventh.
The victory has seen Mayer move up to second in the World Cup downhill standings, 32 points behind leader Aleksander Aamodt Kilde.
'Finally conquers the Stelvio!' - Mayer wins at Bormio for first time