The loss left Monaco, runners-up last season and champions in 2017, second bottom of the standings with 13 points from 17 games, five clear of last-placed Guingamp.
They have conceded 45 goals in all competitions this season, the most by any team in Europe’s top five leagues.
Houssem Aouar scored Lyon’s first after six minutes when he finished off a rebound close to goal and Nabil Fekir made it two 11 minutes before halftime.
Aleksandr Golovin made Monaco’s plight even more difficult when he got a straight red for a bad tackle early in the second half and Ferland Mendy compounded the misery for Thierry Henry’s side when made it 3-0 with a header.
Lyon have 31 points after 17 games, three behind Lille, who moved into second earlier in the day with a 3-2 win at Nimes.
Lille’s first league victory in Nimes since 1954 put the northern side on 34 points from 18 games, three above Lyon and five ahead of fourth-placed Montpellier, who have played two fewer games.
Paris St Germain remain runaway leaders with 44 points from their unbeaten 16-game start.
In Nimes, Rafael Leao put the visitors ahead after five minutes, Jonathan Bamba doubled the with his eighth goal of the season, and Nicolas Pepe got a joint league leading 12th goal after 68 minutes to make it 3-0.
Rachid Alioui got one back for the home side and Clement Depres cut the deficit further in stoppage time with a header, but it was not enough.
Lille’s win came in spite of playing most of the game with 10 men after Jose Fonte was sent off for gesturing to an official after 16 minutes.
Ligue 1 has been disrupted over the last two weeks as several games were postponed because of widespread anti-government protests across France.
With many matches still to be rescheduled, some teams have played two games more than others.
(Reporting by Andrew Downie, editing by Ed Osmond)
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