The three-time World Champion latched on to an attack by Elisa Balsamo (Trek-Segafredo) inside the last 20 kilometres that went clear before dominating the final sprint to win ahead of Kasia Niewiadoma (Canyon-SRAM), Elisa Longo Borghini (Trek-Segafredo) and Silvia Persico (Valcar).
Along with the stage win, Vos becomes the new leader in the overall classification by 10 seconds over Persico in second and Niewiadoma in third as yesterday's leader Lorena Wiebes (Team DSM) slipped to sixth, now 35 seconds behind after finishing with the peloton.
"It's a beautiful day," Vos said after winning her 241st professional stage.
"We knew we had to be focused and alert with one lap to go because it got narrow and the wind played a role, but I didn't expect that we would break away and stay away.
"Elisa Balsamo attacked and apparently it was the moment to go. To take the victory today, it's beautiful and I have to thank my team.
"It was very hard in the final so everybody probably had sore legs, so I knew I just had to go and see if it would be enough."
A very windy day with a high threat of crosswinds got off to an attacking start with Sabrina Stultiens (Liv Racing Xstra), Femke Gerritse (Parkhotel Valkenburg), Rotem Gafinovitz (Roland Cogeas Edelweiss) and Marit Raaijmakers (Human Powered Health) getting in an early break to contest the only climb of the day.
Gerritse took the two points in the Queen of the Mountains classification on offer for the day over the Category 4 Côte de Tigeaux with Raaijmakers taking one, before the peloton ramped up the pace and the group was caught with 78 kilometres to go.
It remained that way for much of the next 40 kilometres on the exposed flat roads with heavy winds raging all day, the bunch spread out but riders staying close together to avoid any splits.
As the roads narrowed into Provins there was a crash with 30 kilometres to go that brought down multiple riders including Australian champion Nicole Frain (ParkHotel Valkenburg) with fellow Australian Anya Louw (AG Insurance-NXTG).
Frain looked relatively unharmed and the race resumed, before she was right in the thick of another crash six kilometres later with Amanda Spratt (BikeExchange-Jayco), this one far more serious.
The rider directly in front of Spratt crashed, causing the Australian to clip her bike and fall in the middle of the road. Still catching back up to the bunch after her earlier fall, a speeding Frain noticed the crash too late, colliding with a downed Spratt and Marta Cavalli (Groupama-FDJ) at high speed.
Both Frain and Cavalli were thrown from their bikes in the collision with the Italian coming off the worst, unable to finish and abandoning the race. Frain came in 86th but Spratt's race took a huge hit as she finished 135th more than nine minutes back.
Another crash with 22 kilometres to brought down Cecilie Uttrup Ludwig (FDJ Suez Futuroscope) before the peloton reached the intermediate sprint, Maike van der Duin (Le Col-Wahoo) crossing first after an earlier attack.
Balsamo attacked shortly after to bridge to van der Duin, the move creating a star-studded breakaway with Vos, Niewiadoma, Longo Borghini and Persico who immediately began to work well together to establish a gap.
With winds still affecting the race, the leaders capitalised on splits and disarray behind to hold a 30-second advantage inside the last 10 kilometres before it went up to 40.5 kilometres from the finish and the peloton were just trying to limit time losses.
Balsamo led the group into the final two kilometres before sitting up for teammate Longo Borghini to attack. Van der Duin attacked through the corner with 400 metres to go but was quickly caught before Vos turned on the speed to win convincingly ahead of Niewiadoma in second and Persico in third.
Ruby Roseman-Gannon (BikeExchange-Jayco) was the best of the Australian finishers in 17th, 35 seconds behind Vos.
The Tour de France Femmes continues with Stage 3, a 133.6 kilometre hilly stage from Reims to Epernay. Watch from the early time of 10:15pm (AEST) on the SBS SKODA Tour Tracker and 10:30pm (AEST) on SBS and SBS On Demand.
