The Malian international Coulibaly headed home five minutes into injury time after Jordan Ferri's early opener for Lyon had been cancelled out by Danijel Milicevic in the first half of a lively game.
Lyon are last in Group H with just one point and cannot now qualify for the Europa League as they lie five points adrift of third-placed Valencia, who lost 2-0 at Zenit St Petersburg as the Russian side continued their perfect run with one game left.
Gent are second on seven points.
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Ferri collected a fine through ball from Rachid Ghezzal before beating Matz Sels at the near post in the seventh minute, giving the home fans some hope for the club's last Champions League game at Gerland.
Sels, however, kept his side afloat 12 minutes later when he denied Alexandre Lacazette after the France international had slalomed through the defence.
The visitors levelled when Milicevic curled a superb 20-metre free kick past Anthony Lopes in the 32nd minute, rewarding Gent's domination.
Lyon had a huge opportunity shortly after the hour but Ghezzal's strike from just inside the box was tipped away by Sels.
Coulibaly wrapped it up for the Belgian side, with a header from close range from the last corner kick of the match.
(Writing by Julien Pretot; Editing by Ian Chadband)
