The 25-year-old Michelton-Scott rider produced a sublime final sprint to give himself a 47 second lead at the top of the leaderboard with 10 stages to go.
ADVERTISEMENTGreat British rider Simon Yates has won the 11th Stage of the Giro d'Italia 2018.
The route stretched 156km from Assisi to Osimo.
The 25-year-old pulled off a sublime late charge over the last 1,500 metres uphill away from nearest challengers Dutchman Tom Dumoulin and Italian Davide Formolo.
It's Yates' second success after winning Stage Nine on Sunday.
Just 8 seconds separated Wedneday's top six at the end of the Giro d'Italia's Stage 11. Fellow Briton Chris Froome fell a further 40 seconds back to 12th place.
Yates' victory puts him top of the leaderboard with 10 stages to go and 47 seconds clear of his nearest challenger, Tom Dumoulin.
He's only the second Brit after Mark Cavendish to win multiple stages of the same Giro.