The 24-year-old Italian Filippo Ganna, together with three other cyclists, had created a gap for other cyclists in the fifth stage, which started in Mileto.
But on the climb up Monte Scuro, he increased his speed and pulled away from the other three.
After a total of 225 kilometers, Ganna was able to cross the finish line 34 seconds ahead of runner-up Patrick Konrad, Australia.
After the victory, Ganna, who runs for the star stable Ineos-Grenadiers, was hugged by the stable that had something to rejoice over after yesterday's adversity.
Yesterday, the favorite and Ineos-Grenadiers captain Geraint Thomas was forced to break the Giro d'Italia after a severe crash in which he suffered a fracture in the hip.
Portuguese Joao Almeida finished third in today's fifth stage and thus retains the pink leader jersey.
Ganna, who before Girot won the World Cup pace at Imolabanan, also won the first stage of the Giro d'Italia and has thus taken two stage victories so far in the competition.