Hubert Fournier's men lost at Lille last time out and looked set for another bad day at the office when Lucas Barrios tapped into an empty net after six minutes.
Alexandre Lacazette restored parity from the penalty spot on the half-hour mark before Nabil Fekir moved Lyon in front with two goals from inside the box either side of the interval.
Barrios squandered a chance to reduce the deficit when he missed an 81st-minute penalty, while Lyon's fourth did not come until second-half stoppage time - Corentin Tolisso bundling home from close range.
There was still time for Lacazette to round off the scoring, though, when he volleyed in unmarked from six yards out.
The result sees Lyon go a point clear of Paris Saint-Germain at the summit.
Coupe de France semi-finalists Saint-Etienne ended a run of seven league matches without a win by triumphing 2-0 over 10-man Lorient.
Didier Ndong received his marching orders for a second bookable offence in the 67th minute, before Yohan Mollo and Max Gradel found the net to earn maximum points.
In the day's remaining fixture, Lille subjected Guingamp to third successive league defeat - winning 1-0 at Stade du Roudourou.
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