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On 13 minutes, Caen threatened again as Andy Delort, reportedly a target for Leicester City, took aim for all of 35 yards, but saw his shot tipped away by the Lille stopper.
However, it was Les Dogues who took the lead on 28 minutes as Djibril Sidibe teed up Benzia, who calmly slotted the ball past Remi Vercoutre.
Early in the second half, Antonetti's men doubled their advantage as Benzia scored his fourth of the season.
Caen did pull one back with 20 minutes left through Delort's penalty after Sofiane Boufal's foul on Sidibe.
However, Lille held on for their first victory under their new manager, which has moved them into 12th place.