Starting the day third 1min 17sec down, the Polish rider attacked a massive 8km from the summit of Mont Ventoux in the Provence region of southern France.
By the time all three main contenders had crossed the line she held a 15sec lead overall on Vollering and Reusser had folded to third overall at 39sec.
"I'm just so tired and so blown away with what just happened," said the stage winner.
"As we started to climb Mont Ventoux, I looked right and I saw my parents. They made a surprise visit, I could see my dad crying, and I was like, 'I just need to make them proud.'"
Niewiadoma won the title in 2024 and took a risky early attack with a track record as the better climer of the three.
The 31-year-old explained her early attack was due to the wind and how it would be harder on the upper lunar landscapes of the mountain to drop the other two.
The Canyon-SRAM rider eventually crested the 1910m altitude finish line 1min 16sec ahead of Dutch rider Vollering with Elisa Longo Borghini third another 26 sec off the pace just ahead of Reusser.
Defending champion Pauline Ferrand-Prevot ended 10 minutes down on the day.
The race ends in Nice on Sunday with the title in the balance on the hills outside the Riviera city.