Annemiek van Vleuten overhauled fellow Dutch rider Anna van der Breggen in the last 25 metres to defend her La Course title in a stunning finale.
Van Vleuten looked beaten when Olympic champion Van der Breggen pulled away on the final climb up Col de la Colombiere and extended her lead on the descent.
But she kept in touch on the run-in and took advantage of a late rise to snatch victory as Van der Breggen faded.
The race is operated by Tour de France organisers ASO.
It saw 112 riders from 20 teams covering the 112.5km ride from Annecy to Le Grand-Bornand, using a similar route to Tuesday’s stage 10 of the men’s Tour.
“With 200 metres to go I thought I was going to come second but then I saw her dying,” said Van Vleuten.
“I always kept on dreaming – I could’ve given up with 500 metres to go but I always believed it was possible. This win is really beautiful.”
South Africa’s Ashleigh Moolman Pasio fell back after initially going away with the Dutch pair on the final climb, but held on to finish third.
Van Vleuten’s resolve sets up thrilling finish
Mitchelton-Scott rider Van Vleuten, 35, was the favourite for victory before the race, but with 100 metres to go it looked like she would relinquish the title to her 28-year-old compatriot, riding for Boels-Dolmans.
Yet just 50 metres later she was level, dancing on the pedals to kick past Van der Breggen, who had nothing left, having admirably kept the world time trial champion at bay on a flat final section after a high-speed descent.
It was a role reversal from the upper slopes of the Col de la Colombiere, when Van der Breggen’s decision not to ride the Giro Rosa stage race, which Van Vleuten won on Sunday, looked to have paid off as she kicked clear of her rivals to cross the summit alone.
Van Vleuten momentarily looked spent, but dug in, showing the resolve that has seen her establish herself as one of the sport’s most dominant riders since recovering from three spinal fractures sustained in a horrific crash in the Rio Olympics road race.
“I knew I was in good shape but Anna is a really good cyclist – it was tough but to win this way is so beautiful,” she said.
“Together with last year’s win, winning the Giro Rosa on Sunday and then this, it’s really high on my list.”
Room to expand?
La Course reverted to single stage this year, having been a two-day event in 2017 following three iterations held in Paris since its inception in 2014.
Some current and former professionals criticised the decision, though many also acknowledged that for the first time the route contained four categorised climbs and was run over a longer distance – last year’s first stage on the Col d’Izoard was just 65km.
There is also a debate over the feasibility of running a women’s stage-race on the same day and over the same courses as the men’s Tour, but the benefit of the crowds already being on the roadside was evident here.
“The people watching us, calling my name, cheering us on, it was crazy – it was one of the best days of my life,” said Denmark’s Cecilie Uttrup Ludwig, who held on for fourth after a fine solo attack over the top of the penultimate climb, the Col de Romme.
While many of the world’s top female riders competed here, most had also only finished a tough Giro Rosa, considered the most prestigious women’s stage race, on Sunday.
“We were all tired after the Giro Rosa but we just had to ride with our hearts,” Australia’s Amanda Spratt, who finished eighth, told ITV4.
“I like that it was a proper mountain stage and I’m grateful for that, but we want to be pushing for more days and a full Tour would be great.”
1. Annemiek van Vleuten (Ned/Mitchelton-Scott) 3hrs 20mins 43secs
2. Anna van der Breggen (Ned/Boels-Dolmans) +1sec
3. Ashleigh Moolman Pasio (SA/Cervelo-Bigla) +1min 22secs
4. Cecilie Uttrup Ludwig (Den/Cervelo-Bigla) +1min 58secs
5. Megan Guarnier (US/Boels-Dolmans) +2mins 19secs
6. Katarzyna Niewiadoma (Pol/Canyon SRAM) same time
7. Katharine Hill (US/UnitedHealthcare) +2mins 22secs
8. Amanda Spratt (Aus/Mitchelton-Scott) same time
9. Ane Santesteban Gonzalez (Spa/Ale Cipollini) +2mins 24secs
10. Erica Magnaldi (Ita/Bepink) same time