Several crashes had splintered the peloton in the final 25km of the 135km run to Provins, east of Paris, and Vos found herself in a six-rider escape bunch.
With general classification rivals Elisa Longo Borghini (30) and Katarzyna Niewiadoma (27) also in the group, Vos showed her class to sprint clear to cross the line comfortably ahead.
Silvia Persico (25, Valcar-Traval & Service) was second with Neiwiadoma (Canyon/Sram Racing) in third place. The top three on the stage now fill out the top three in the general classification.
Fellow Dutch rider Lorena Wiebes (23) had been favourite to follow up her victory on the Champs Elysees on Sunday's opening stage but came home in the second group.
There was heartache for one of the race favourites Marta Cavalli (24) of Italy who abandoned after being involved in a high-speed pile-up towards the end of the stage.
Cavalli rode straight into a pile of bikes and riders laying in the middle of the road and was launched across the tarmac.