Slovenian superstar Pogacar's triumph was built by his UAE Team on the ascent of the Galibier mountain with three teammates still with their leader when all their rivals had seen their sherpas dropped.
Belgian Quick Step rider Remco Evenepoel finished second 35 seconds off the pace with two-time defending champion Jonas Vingegaard of Denmark finishing fifth at 37sec.
Vingegaard's Visma team appeared visibly weaker than during their dominant 2023 showcase second triumph on the Tour.
Overnight leader, Education First's Richard Carapaz, was the big loser of the day as the Ecuadorian gave up over five minutes.
Pogacar, winner in 2020 and 2021, is attempting to become the first rider since 1998 to win both the Giro d'Italia and Tour in the same year.
The short 134km run from Pinerolo marked the end of an entertaining and picturesque race start in Italy.
The first four stages took in Florence, the Adriatic coast, Bologna and the Piedmont region on the French border beside Turin.
Pogacar's Team UAE hogged the front of the 25km final ascent taking it in turns on the front as their rivals wilted.
Runner-up in the past two editions behind Vingegaard, Pogacar attacked less than 1km from the summit, and it was the last his rivals saw of him so winding was the route.
Massed ranks of fans, many of whom had camped overnight, packed the roadsides all the way up the magnificent beyond category mountain.
On Wednesday, stage five will see Biniam Girmay, Jasper Philipsen, Mark Cavendish and the fast men jostle for position as the 177km snakes through valleys between Saint-Jean-de-Maurienne and the village of Saint-Vulbas.
