The UAE Team Emirates XRG star attacked the leading group, including Jonas Vingegaard and Paul Seixas, with seven kilometres left of the punishing 155.3km day from Mulhouse to Le Markstein, as none of his rivals could contend with his acceleration.
It was a one-two for Pogacar's team, with Isaac Del Toro taking second, whilst young French hope, Seixas, rounding off the podium.
Denmark's Vingegaard finished fourth - 44 seconds adrift of Pogacar, who emulated his 2023 victory on the same finish.
His lead in the general classification now sits at 4:30 from the Dane, whilst Remco Evenepoel remains third, despite being dropped on Col du Haag, a further 34 seconds back.
Seixas moved into the white jersey thanks to taking 16 seconds from Juan Ayuso, whilst Pogacar remains in the king of the mountains jersey.
The stage started in apocalyptic conditions with torrential rain greeting the riders as they rolled through kilometre zero. That, and the intermediate sprint after just 12 kilometres of racing, neutralised the opening stages.
After Jasper Philipsen chipped a few more points away from green jersey leader, Mads Pedersen, the attacks began on the first climb of the day - the 20-kilometre slog up the Grand Ballon.
Tom Pidcock, fourth in general classification overnight, was the standout rider to go in the 24-man breakaway alongside Richard Carapaz, Tobias Halland Johannessen and French hope on the day, Valentin Paret-Peintre.
The latter would take the mountain points over the top of the category one climb, skipping away with Carapaz as the descent started. They would be joined by the Halland Johannessen twins, Ben Healy, with Einer Rubio also tagging on.
The quintet were never given more than three minutes by UAE Team Emirates XRG as Pogacar looked for another stage win.
Paret-Peintre and Rubio were dropped on the lower slopes of the final climb of the day as Carapaz and Halland Johannessen kept on pushing, but their efforts were for nothing as they were caught with 8.2 km to go thanks to a vicious pace from Vingegaard.
All that allowed was Pogacar to ride away, demonstrating his dominant presence at this race once again.