With two tough stages remaining, the 2020 and 2021 Tour de France champion Pogacar leads Vingegaard by 5min 03sec while Remco Evenepoel remains third now at 7min 01sec.
Pogacar is also two stages away from a Giro d'Italia and Tour de France double, which would be a first in 25 years.
A dominant and confident Pogacar promised to attack here on the Queen stage with its massive mountains and came into stage 19 with a 3min 11sec lead over Vingegaard, with Evenepoel at 5min 11sec in third.
Previous weak moments for the Team UAE rider have come at altitude and in hot weather as he let slip the Tour de France title to the Dane Vingegaard.
So the 25-year-old will have been happy riding under overcast skies as the mercury dipped to 18.5C (65f).
There was plenty of altitude on the menu however as the pack first crossed the fan packed Col de la Bonnette, a 23km climb at 7 percent average gradient to the dizzying altitude of 2800m.
The final climb to Isola 2000 ski resort is hardly less crushing and Pogacar attacked with a jaw dropping 10km to go.
He left his rivals trailing in his wake and chewed up the attackers one by one in quick succession.
Matteo Jorgenson was second on the day at 21sec, Simon Yates had led much of the way but dropped to third at 40sec after Pogacar passed him
Richard Carapaz was fourth at 1min 11sec and Evenepoel fifth with Vingeaard on his wheel.
Eritrean break out star Biniam Girmay retained the green sprint jersey ahead of Jasper Philipsen as the escape group took the intermediate sprint points way ahead of the peloton.
Girmay and Philipsen have both won three stages, while Pogacar has four.
