This famous old ground has been a fortress in the UEL in recent years, and the hosts were clearly intent on using the atmosphere to give them an early advantage.
Inside the opening 10 minutes, James Tavernier had a close-range volley saved by Lucas Perri before Vaclav Cerny inexplicably fired a rebound over the bar with the goal at his mercy.
Rangers were immediately punished, as Les Gones showcased some incredibly intricate build-up play to break the deadlock.
Rayan Cherki was pulling the strings, with his mazy run eventually ending with Malick Fofana expertly finding the bottom corner to break the deadlock.
Just four minutes later, however, Philippe Clement’s men restored parity.
A catastrophic mix-up at the back saw Corentin Tolisso’s attempted header back to his goalkeeper cut out by Cyriel Dessers, allowing Tom Lawrence to steal in and fire past Perri.
The hosts’ jubilance would also be short-lived though, with Lyon re-establishing the lead as they were the beneficiary of a defensive error.
Connor Barron attempted a blind square pass on the halfway line which was intercepted, and the visitors’ electric attack made him pay as Fofana raced away before squaring for Alexandre Lacazette to slide home.
Getting to the interval without conceding further damage was imperative to Rangers, but a moment of Lyon brilliance in stoppage time put paid to those ambitions.
Lacazette received the ball on the edge of the area and rifled a gorgeous strike into the top corner to truly take the sting out of the Ibrox crowd.
Things got no better for the home side after the restart, losing goalscorer Lawrence to injury before falling three goals behind.
Cherki’s magical footwork helped him dance to the byline and square for Fofana, who converted at the back post to put the contest well beyond the Scottish giants.
It’s another chastening night for Scottish football in Europe, coming 48 hours after Celtic were beaten 7-1 by Borussia Dortmund.
Rangers’ four-game winning run comes to an abrupt end, while Lyon extend their unbeaten away run in the UEL to eight matches with a performance that sends out a statement of intent to the rest of the competition.