Swiss champions Basel go through 4-3 on aggregate.
Lyon entered Tuesday's second leg at the Letzigrund Stadium with a one-goal advantage after a narrow win in France last week, and Remi Garde's side moved a step closer to a return to the group stage as Clement Grenier struck a late winner to cement their place in the next round.
Michael Lang had the best chance of a quiet first half, but the defender was thwarted by a combination of Bakary Kone and goalkeeper Anthony Lopes having initally breached the Lyon backline.
Nzuzi Toko then tested Lopes with an angled strike just prior to half-time, while Alexandre Lacazette fired low at Roman Bürki after wriggling free on the edge of the box in what represented Lyon's best effort prior to Grenier's goal eight minutes from time.
Samuel Umtiti intercepted a loose pass, picking out Gueida Fofana who set Lisandro Lopez free before the Argentine squared for Grenier to slot past Bürki to cap off a clinical counterattack.
Earlier, Fenerbahce clinched their place in the final qualifying round after coming from a goal down to beat Austria's Red Bull Salzburg 3-1 in Istanbul for a 4-2 victory on aggregate.
Jonathan Soriano put the visitors into a fourth-minute lead, but Raul Meireles levelled for Fenerbahce shortly after before Moussa Sow and Pierre Webo gave the Turkish giants to a two-goal lead that they would not relinquish.
Meanwhile, Basel played out a thrilling 3-3 draw with Maccabi Tel-Aviv in Israel, a result that put the Swiss champions through 4-3 on aggregate.
Fabian Schär handed Basel an early lead from the penalty spot with subsequent strikes from Mohamed Salah and Marcelo Diaz putting the visitors in firm control.
However, they were made to face an anxious final half-hour after Schär first put through his own net before both Eran Zahavi and Maharan Radi got on the scoresheet to haul Maccabi level on the night.