Monaco coach Didier Deschamps stated before the game that the competition was not his priority but his charges did the business in devastating fashion.
There seemed little prospect of a home win when Giovane Elber put Lyon in front on 14 minutes.
From then on, however, the game belonged to Fernando Morientes who netted three goals in a 15-minute spell either side of half time to stun Lyon.
The Spaniard's first came on the stroke of half time as he left Edmilson in his wake before slamming a shot into the top corner from 20 yards.
The goal buoyed Monaco who grabbed a second, through Morientes, on 58 minutes. The Spaniard completed his treble shortly after the hour mark.
Lyon were by now in complete disarray and Dado Prso headed home a fourth five minutes from time to cap a great night for Monaco.
Nantes sidestepped a potential banana-skin when proving far too classy for Brest. Viorel Moldovan netted a brace with the other goals coming from Loic Pailleres and Gregory Pujol.
Two games went to penalties, with Rennes getting the better of Toulouse and Dijon seeing off Reims.
Chateauroux beat Creteil 2-0, while Amiens edged past Caen 1-0.
