In one of modern cycling's most memorable individual performances, the 25-year-old Vacansoleil-DCM all-rounder attacked from a breakaway on the fabled Alpine pass to take the illustrious Cima Coppi prize - and move into fourth place in the general classification, two minutes and 18 seconds behind race leader Joaquim Rodriguez of Spain.
Rodriguez finished the 219km stage from Caldes in fourth place, 3:22 down on De Gendt, to consolidate his pink jersey. The Katusha climber gained 14 seconds on Canada's Ryder Hesjedal in the GC after distancing the Garmin-Barracuda rider in the closing moments of a thrilling stage.
Hesjedal is now 31 seconds down on Rodriguez ahead of Sunday's deciding 30km time trial in Milan, with defending champion Michele Scarponi (Lampre) up to third place, 1:51 in arrears.
But the day belonged to De Gendt who put on a display of outlandish attacking so reminiscent of his compatriot, the great Eddy Merckx.
Starting the day almost six minutes down on Rodriguez and in eighth place in the GC, De Gendt was part of the select group that had formed around the maglia rosa on the first of two legendary climbs that concluded the stage, the Cat.1 Mortirolo.
A large group of 14 riders – including Friday’s winner Roman Kreuziger (Astana) – had broken clear of the peloton after just 22km of racing on the first of three classified climbs in the opening half of the race’s queen stage.
From the inItial group, Switzerland’s Oliver Zaugg (RadioShack Nissan) broke clear at the start of the punishing Mortirolo – once described by Lance Armstrong as “the hardest climb I have ever ridden”.
While Zaugg rode clear from a chasing group of four riders, further down the hill the main pack had been considerably trimmed after an early dig by the pink jersey Rodriguez.
Approaching the summit, De Gendt made his move – attacking on one of the narrow asphalt sections of road that boasts a brutal gradient of 22 per cent.
Zaugg crossed the summit of the Mortirolo in pole position to pick up the Cima Pantani – a prize dedicated to the memory of the late Marco Pantani, whose finest performance in the Giro came on his devastating ascent of the same climb in 1994.
De Gendt passed over the top around three minutes down and soon caught the remnants of the day’s initial break on the fast descent.
In the valley between the two major climbs of the Mortirolo and Stelvio, the De Gendt leading group was joined by two Euskaltel riders – Mikel Nieve and Jon Izagirre – as well as Astana’s Tanel Kangert and the 2004 Giro champion, Damiano Cunego (Lampre).
An exhausted Zaugg was caught with 30km remaining as the seven-man leading group rode 3:40 clear of the pink jersey chasing group.
Moments into the final 22km climb to the summit, Zaugg was the first to crack and was soon followed by stage 16 winner Izagirre, Kangert and Movistar’s Andrey Amador, the Costa Rican winner of stage 14.
De Gendt’s initial attack was foiled only by Nieve, as Cunego became slightly distanced. Although Nieve was celebrating his 27th birthday, his Belgian colleague was not in the mood to give him any gifts, waving the Spaniard through to help set the pace as a resurgent Cunego slowly returned to their wheels.
Then De Gendt made his decisive move, attacking unexpectedly in a tunnel – still a huge 13km from the finish.
What the world then witnessed will go down as one of the great moments in the Giro’s history as De Gendt not only rode clear of his fellow escapees, but also increased his lead over the main chasing group at an alarming rate.
At one moment just inside the final 10km, De Gendt was a huge 5:35 ahead of the Rodriguez group – putting the Belgian within five seconds of the virtual pink jersey.
With De Gendt looking more and more assured, the win quickly became a certainty; the question was how much time the outsider could take from the ostensible race favourites.
Back with the main group, it was left to Canadian Hesjedal – himself considered an outsider at the start of the race – to lead the chase.
Italy’s Ivan Basso (Liquigas) and Colombian Rigoberto Uran (Team Sky) were first to fade, swiftly followed by the diminutive climber Domenico Pozzovivo (Colnago).
As De Gendt completed the final few snow-capped hairpin bends (the Stelvio boasts a total of 40 such corners) Scarponi made an attack further down the mountain, dropping both Hesjedal and Rodriguez.
De Gendt secured the biggest win of his career with outstretched arms and a huge grin. The Belgian youngster completed the gruelling stage in a time of six hours 54 minutes and 41 seconds to take the Cima Coppi prize, named after the legendary Italian rider Fausto Coppi, who once thought he “was going to die” while climbing the Stelvio during the 1953 Giro.
Cunego held on to take second place, 56 seconds off the pace, while Nieve secured third, 2:50 down.
But a late attack by the pink jersey saw Rodriguez distance Hesjedal and pass Scarponi in the final 500 metres, the Spaniard finishing fourth, 3:22 behind De Gendt.
Scarponi crossed the line for fifth at 3:54, two seconds ahead of Hesjedal, who will now enter the final ITT in Milan needing to overturn a 31-second deficit on race leader Rodriguez.
Scarponi consolidated his third place in the GC after Basso could only finish 10th on the stage, 4:54 down.
But the defending champion will have to look over his shoulder at De Gendt during Sunday’s time trial, with Belgium’s new hero a real threat for the final podium position.
De Gendt, a far stronger time triallist than both Scarponi and Rodriguez, is now fourth at 2:18.
Should Rodriguez miss out on the pink jersey in Milan, the Spaniard will take consolation with the red points jersey, which he secured on Saturday with his fourth-place finish, overturning Team Sky sprinter Mark Cavendish’s lead by one slender point.
Italy's Matteo Rabottini (Farnese Vini) secured the red jersey mountains classification in his debut Giro on Saturday by taking maximum points over the opening the classified climbs.