The principality side, who had held a 10-point lead over Olympique Lyonnais six weeks ago, now trail Bruno Genesio's side on goal difference. Both team are on 55 points with five games left.
Morgan Amalfitano opened the scoring in the 37th minute with Eder doubling the tally in the 67th. Mounir Obbadi put the result beyond doubt in the 77th and Djibril Sidibe added to Monaco's misery with a fourth two minutes from time.
Fares Bahlouli pulled one back for the visitors in added time.
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Both teams finished with 10 men after Lille's Renato Civelli was sent off in the 55th and Monaco's Elderson Echiejile picked up a red card 10 minutes later.
(Reporting by Julien Pretot, editing by Pritha Sarkar)
