With qualification for the knockout stages already assured, the Spaniards were banking on BATE Borisov pulling off a shock at Bayern Munich in order to top the group, but in the end had to settle for second place.
A low-key start saw the home side have the best of what passed for the few early chances, with Franck Beria's second minute shot blocked by Rodriguez Salva Ruiz in the box.
Valencia came closer in the 17th minute when Beria's foul on Andres Guardado allowed Miguel Costa to float a free-kick into the Lille box where Adil Rami's header was saved by home keeper Steve Elana.
Lille had their own chance from a set-piece five minutes later when Lucas Digne floated in a free-kick from the right and Marko Basa's close-range header was directed just over the bar.
Elana saved a long-range effort from Jonas then Lille responded by bringing Valencia keeper Vicente Guaita into the game for the first time to save a 20-yard effort from Antonio Mavuba.
Salomon Kalou shot over the bar and Florent Balmont brought another save out of Guaita as the home side enjoyed their best spell of the game around the half-hour mark.
But minutes later Lille fell behind when Basa fouled Jonas in the box and the same player picked himself up to slam a powerful spot-kick past Elana.
Sofiane Feghouli could have made it 2-0 five minutes later as Valencia continued to press, but it was Lille who had the better of the early second half action, with both Ronny Rodelin and Gianni Bruno coming close.
Serious pressure from the home side saw Guaita pluck a dangerous Marvin Martin corner from the air, then Bruno should have done better with a header from 12 yards which flashed just left of Guaita's goal.
News of Bayern's easy win rendered the late action rather obsolete, but Jonas came close to adding a second before Dimitrie Payet almost stole a late point for Lille with a right-footed drive which rebounded off Guaita's bar.