The 33-year-old, who won the Paris-Roubaix Femmes in April, attacked seven kilometres from the summit to overtake Niamh Fisher-Black (Lidl–Trek) and Yara Kastelijn (Fenix–Deceuninck) before riding clear.
The Visma–Lease a Bike rider crossed the line one minute and 45 seconds ahead of Sarah Gigante (AG Insurance–Soudal), with Fisher‑Black in third, two minutes and 15 seconds behind.
"It was super painful, the last kilometre, because I wanted to have a gap as big as possible for tomorrow. I also wanted to enjoy it, but it's not over until you cross the finish line. I’m so happy we made it," Ferrand-Prevot said.
Ferrand-Prevot's Visma teammate Marion Bunel, who was with her in the early breakaway, dropped back to pace her on the Col de la Madeleine.
"I can't wait to see my teammates and to share this jersey with them because they have been a big, big part of this victory and this yellow jersey," Ferrand-Prevot added.
"For sure I will give everything for the jersey tomorrow. My teammates will be there to support me, so it makes me feel a bit more relaxed about it."
Ferrand-Prevot, Paris Olympics gold medallist in cross-country mountain biking, will take her commanding lead into Sunday's final stage, aiming to become the first Frenchwoman to win the Tour de France Femmes.
It was a third straight stage victory for France, which capped an aggressive display from Ferrand-Prevot, who started the day 26 seconds off the general classification leader Kimberley Le Court Pienaar (AG Insurance-Soudal).
Her win put her in the overall lead, with Gigante, two minutes 37 seconds adrift, the only general classification favourite still able to challenge her on the final 124.1km mountain ride from Praz-sur-Arly to Chatel.
Mauritian Le Court crashed on the descent from the Col du Frene with 63km remaining, briefly trailing the peloton by about a minute before resuming her chase.
She rejoined later, but her effort to set the pace for teammate Gigante, combined with the relentless climbing, cost her dearly in the general classification, dropping her to 11th place.