Van Vleuten broke clear from the peloton on the early slopes of the Planche des Belles Filles, the yellow jersey immediately getting a gap and solidly increasing her lead all the way to the finish to win in style.
Demi Vollering (SD-Worx) finished in second to confirm her second place overall while Silvia Persico (Valcar-Travel & Service) was fastest from a small group behind to finish third on the day.
"To win in Yellow, especially at La Planche des Belles Filles, that’s something I wanted since we did the recon," said van Vleuten. "That was the best I could think to finish it off. I enjoyed it a lot with all the spectators shouting when I was riding up and also coming down.
"After being sick on days 2 and 3, I can’t believe I’m here with the jersey. It made it crazy hard.
"I felt part of the Tour. I think it was a great way to start the first edition of the Tour de France Femmes avec Zwift. And I think we can build from here for the next years."
A group of 10 talented riders went clear after an aggressive start to the race, with Australian Grace Brown (FDJ-SUEZ-Futuroscope) present in the move that jumped clear with 68 kilometres remaining in the race.
Annemiek van Vleuten suffered a mechanical issue with 57 kilometres remaining on the stage, changing quickly onto teammate Arlenis Sierra’s bike and setting off again. In situations like this involving the race leader in a stage race, the other teams normally respect that it was a matter of bad luck and wait up for the leader to return.
However, SD-Worx and Trek-Segafredo went to the front of the peloton and drove a hard tempo, enough that they dragged back almost all of the 1’50 gap to the breakaway that had escaped at the head of the race. Van Vleuten had to ride hard on her borrowed bike to catch up to the fast-moving peloton, flying over to the group on the early slopes of the penultimate climb of the Ballon d'Alsace.
She then pointedly went to the front of the group and put her hand up for the team car so no one could claim they hadn’t seen her and swapped onto her spare bike, though she would change her bike again just a few kilometres later.
The pace backed off, and the leaders pushed out their lead from what had been a slim 15 second advantage to a minute and a half with just a few kilometres left to climb. At that point, Vollering attacked on two occasions and drove the pace, though most of the favourites were able to respond, and the pace slackened again.
Off the back off a lull in the main bunch’s tempo in the valley approaching the Planche des Belles Filles, Rachel Neylan (Cofidis) put in a big attack to try and bridge the one minute gap to the breakaway, though she wasn’t able to catch the front riders.
The breakaway arrived at the foot of the Planche des Belle Filles with a gap of 20 seconds on the peloton and still the hardest climbing on the day to do on the 7 kilometre and 8.7 per cent climb.
Pauliena Rooijakers (Canyon-SRAM) was the first to attack at the foot of the climb, with Annemiek van Vleuten (Movistar) not far behind as she opened out a lead on her rivals, jumping over to teammate Paulo Patino who did a short, hard turn for van Vleuten before dropping off.
Van Vleuten danced up the climb, catching and dropping Rooijakers at the front of the race with Vollering the primary rider in pursuit. Niewiadoma led the next group on the road with Juliette Labous (Team DSM) also contributing to the chase in the fight for the final spot on the Tour de France Femmes podium.
The yellow jersey crossed the finish line atop the Planche des Belles Filles first, 30 seconds ahead of Vollering, with Silvia Persico (Valcar-Travel & Service) battling through to third 1’43 behind.
The final podium of van Vleuten, Vollering and Niewiadoma was confirmed, with the mountains jersey going to Vollering, the young rider’s classification to Shirin van Anrooij (Trek-Segafredo), the points jersey to Marianne Vos (Jumbo-Visma) and the teams classification to Canyon-SRAM.
