Turkish forward Yusuf Yazici's breathtaking volley gave the visitors a 17th minute lead followed by strikes for Jonathan Bamba near halftime and defender Tiago Djalo midway through the second period.
Jonathan David's late penalty hit the post to deny Lille a fourth goal after they had been handed a 7-1 home drubbing by champions PSG last Sunday.
Cyrille Bayala had pulled one back for Ajaccio as Lille failed to clear a corner six minutes from time.
Lille are fourth with seven points, two behind leaders PSG who host AS Monaco on Sunday, while Ajaccio are third-bottom on one point and still looking for a first victory since their top-flight return after relegation in 2014.
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