The two-time Tour de France champion, who is bidding to complete a career sweep of the three Grand Tours after winning last year’s Vuelta a Espana, finished 13 seconds clear of Felix Gall to complete his set of stage wins on all three of the 21-day races.
Former Giro winner Jai Hindley of Australia was a further 49 seconds back in third place.
“Today we just wanted to go for the win and I’m extremely happy that I was able to finish it off,” said Visma’s Vingegaard. “My teammates did an amazing job today.”
Vingegaard’s first Giro stage win laid down a serious marker to the field in his race debut.
He was over six minutes behind overall leader Afonso Eulalio heading into the day, but took almost three minutes out of that advantage.
The Dane is now second in the general classification, 3min and 17sec behind Eulalio and 17sec clear of third-placed Gall.
“I’m definitely happy that I could take back some time,” added Vingegaard.
“It was a good day for me, a good day for us… To take back some time on my opponents, it’s a good day for us.”
Portuguese rider Eulalio took the pink jersey by winning a rain-lashed fifth stage earlier this week.
Friday’s race developed on the brutal final Blockhaus climb with winds buffeting the riders, a 13.6km ascent with an average 8.4-percent gradient.
Former Tour de France winner Egan Bernal and Movistar’s Enric Mas were both dropped by an ever-shrinking peloton.
Vingegaard attacked with six kilometres remaining, dropping Eulalio, with only Giulio Pellizzari able to follow the Visma team leader.
The Dane attacked again on the steepest part of the climb, though, and this time Pellizzari was unable to keep pace.
The 29-year-old managed to stay ahead of a fast-finishing Gall, although the Austrian dug deep to limit the time lost.
“At first I was a bit annoyed that I couldn’t follow the Italian and Jonas, but in the end it was the right choice and it was good that I did my own pace,” said Gall.
Eulalio crossed the line two minutes and 55 seconds behind, two seconds ahead of Bernal, achieving his goal of holding onto the pink jersey heading into Saturday’s 156km eighth stage from Chieti to Fermo.
“It was one of the objectives for today,” said Eulalio. “I tried to suffer as much as possible.”
Pellizzari paid for his efforts to stay with Vingegaard, finishing fourth on the day.
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