Goals from Bafetimbi Gomis and Jordan Ferri have ensured that Lyon leave Stade du Hainaut with all three points.
The visitors were ahead just short of the half-hour mark courtesy of Gomis, who made no mistake in finding the back of the net from inside the box.
Valenciennes levelled the contest in the second half after hitting Les Gones on the counter, leaving Majeed Waris to make it 1-1 on 66 minutes.
Just three minutes later Lyon were back in front, this time Ferri striking from distance to put Remi Garde's side on course for victory.
Both teams were reduced to 10 men when Remy Vercoutre and Marco da Silva were dismissed within the space of three minutes of each other late on, and Valenciennes could have levelled with two minutes remaining, but Waris missed from the penalty spot to ensure that Lyon left with the points.
