The 31-year-old won the 146.8 km stage from La Voulte-sur-Rhône to the summit of Mont Ventoux in southern France.
She took the yellow jersey after breaking away from her rivals with eight kilometres remaining and gradually extending her lead, Polish state news agency PAP reported.
It was Niewiadoma-Phinney's first stage victory since 2019, when she won a stage of the Tour of Britain. She won the women's Tour de France overall in 2024 and is seeking to capture another title.
"Kasia Niewiadoma-Phinney leads the Tour de France after a brilliant stage victory," Polish Prime Minister Donald Tusk wrote on social media.
Niewiadoma-Phinney leads the overall standings by 15 seconds over Dutch rider Demi Vollering, who finished second on Friday, and by 39 seconds over Switzerland's Marlen Reusser.
Katarzyna Niewiadoma. Photo: Darek Matyja/Polish Radio
Saturday's penultimate stage covers 171.9 km from Sisteron to Nice.
The race finishes on Sunday wit a 99.2 km mountain stage beginning and ending in Nice.
Niewiadoma-Phinney finished third overall in the Tour de France in 2023, matching her result from 2022. She also won the Queen of the Mountains jersey as the race's best climber in 2023.
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Source: IAR, PAP