Visma's Jonas Vingegaard was second, doggedly staying right on Pogacar's wheel to the line with Briton Oscar Onley third after a late nine-rider pile-up marred the finale.
On his 19th career Tour de France stage win, the 26-year-old Pogacar gained four seconds on Vingegaard with ten bonus seconds to the Dane's six.
"It was super-hot today, and super fast, but we had a plan and we stuck to it," said the Team UAE rider who was champion in 2021, 2022 and 2024.
In the overall standings, Remco Evenepoel is second, 54 seconds off first as he came sixth on the day, two seconds adrift.
"The Tour de France isn't over yet," said Evenepoel, who lost time in a crosswind on stage one before winning the stage five individual time-trial.
French starlet Kevin Vauquelin continues his bright run in third at one minute, 11 seconds, while two-time champion Vingegaard is fourth at one minute, 17.
Fans cheered for Vauquelin along much of the route. On Thursday, a hot-air balloon flew over the peloton with his face on it.
"All you could hear was 'Kevin, Kevin' all along the road, it's so good to have a new face competing with us," said Pogacar.
The overnight leader, Mathieu van der Poel, rounds out the top five at one minute, 29 seconds, after wilting on the final climb, scene of his 2021 coming-of-age win and his first yellow jersey.
"Matthieu and I both wanted to win on this iconic climb, but maybe he left too much on the road yesterday," Pogacar said of his friend Van der Poel, who climbed top of the overall rankings Thursday.
The day's action revolved around two ascents of the Mur de Bretagne, a 2km climb at an average of six per cent, that has been written into Tour de France folklore.
With the Tour returning to Brittany after a four-year gap, huge festive crowds packed the villages and pretty country lanes as the temperature hit 30 Celsius.
The 179 remaining riders left Saint Malo on the north-west coast, passing the magnificent Sillon beach with its granite sea-wall and chic sea-front buildings.
Fewer of them will take the start line for Saturday's flat run to Laval, with doubts over key Pogacar teammate Joao Almeida and the Colombian Santiago Buitrago.
"I really hope he's okay, he's on his way for an X-ray. I'm proud of how he's been riding. He's done an amazing job. It would have been a perfect day," Pogacar said of Almeida's fall ahead of the second climb of the Mur de Bretagne.