Valencia - Gary Neville endured the worst possible start to his managerial career as Valencia crashed out of the Champions League due to a 2-0 home defeat to the already eliminated Lyon on Wednesday.
Goals either side of half-time by Maxwel Cornet on his first Champions League start and Alexandre Lacazette handed the French side their first European win of the season.
Belgian champions Gent beat Zenit St Petersburg 2-1 to seal their place in the last 16 behind the Russians in Group H.
England coach Neville was set for a baptism of fire after his surprise appointment last week with Valencia needing to win and Gent to drop points to seal their place in the last 16 for the first time in three years.
The former Manchester United defender made just two changes from the side that held European champions Barcelona to a 1-1 on Saturday with Joao Cancelo returning from suspension and Shkodran Mustafi fit again to take his place at the heart of the defence.
And Mustafi was desperately unlucky not to get Neville off to a flying start inside 10 minutes as he thundered a header off the post and was then penalised for a foul when he did find the net from Valencia's next corner.
Lyon were already eliminated from all European competitions and hadn't won any of their last five games in all tournaments.
However, the visitors produced an impressive display and Valencia had to count on goalkeeper Jaume Domenech to keep them in the game.
Domenech's first fine save came on 11 minutes when he turned Cornet's effort to safety as the 19-year-old bore down on goal.
Valencia started the evening without eight first team players through injury and they suffered another setback when Argentina international Enzo Perez hobbled off to be replaced by Javi Fuego.
Domenech had to come to Valencia's rescue twice more in quick succession as he denied Corentin Tolisso and Rafael da Silva.
At the other end, Lyon 'keeper Anthony Lopes showed he was just as capable of pulling off a big save as he flew to his left to parry Paco Alcacer's header.
However, Lyon were handed the half-time lead they deserved by Cornet's stunning solo effort nine minutes before the break as he cut inside before firing into the top corner via a slight deflection off Aymen Abdennour.
Neville made a bold move at the start of the second period by throwing on Alvaro Negredo for his first appearance in over two months in place of the more defensively minded Danilo.
Yet, despite the home fans roaring on their side with encouragement after Zenit briefly restored parity against Gent, it was Lyon who again posed the greater threat after the break on the counter-attack.
Lacazette blasted over from close range before he played in Sergi Darder with a wonderfully timed pass, but the former Malaga midfielder was denied by another fine stop from Domenech.
There was nothing the Valencia stopper could do 15 minutes from time, though, as Lacazette was released in behind the defence and the French international sprinted beyond Abdennour before slotting home his second Champions League goal of the season.