The hosts began the night six points adrift of Lyon, but swept aside their French visitors in the early going with first-half goals from Alan Kardec, Fabio Coentrao and Javi Garcia.
Coentrao's second made it 4-0 midway through the second half before Lyon began their fightback.
Yoann Gourcuff got the first before Bafetimbi Gomis struck five minutes from time.
Dejan Lovren headed home in the fifth minute of injury time, but the points went to Benfica.
Jorge Carlos Martins provided the assist for all four Benfica goals.
The hosts dominated the opening half, piling pressure on Hugo Lloris' goal.
Maxi Pereria's early sighters began the assualt before Coentrao fired narrowly over from close range.
They opened the scoring in the 19th minute with Martins whipping in a free-kick which Kardec headed home.
Lyon were not seen as an attacking force until the 28th minute, when Jimmy Briand blazed over from Anthony Reveillere's cross.
And moments later the visitors found themselves 2-0 down when Coentrao volleyed home from another Martins cross.
Cris had a great chance to get Lyon back into it seven minutes before the break, but headed narrowly wide from Gourcuff's free-kick.
At the other end, Lloris parried Javier Saviola's close-range shot away.
But Benfica would get a third before half-time as Martins' corner found Javi Garcia who headed home.
Lyon began the second half brighter, with chances falling for Briand early on.
But he failed to take either, and instead Benfica took a 4-0 lead.
Martins was the provider but Coentrao took the plaudits as he lobbed the goalkeeper from 20 yards.
Martins would not get a goal himself though, firing wide with his final chance before being replaced with a little over 15 minutes to go.
Perhaps it was no coincidence that the Lyon fightback then began.
Alexandre Lacazette's cross found Gourcuff who lashed home the first in the 75th minute.
Lovren then headed just over from Gourcuff's corner before Gomis got a second five minutes from time, finishing easily from Lacazette's cross.
There was enough injury time for Lovren to head home at the death, but Lyon had left their fightback too late.
With Schalke held to a draw by Hapoel Tel Aviv, Benfica move to within a point of the top two in the group.