Lille put the visitors on the back foot in the opening minutes and enjoyed large spells of possession.
The first goal of the game came in the 15th minute as Yoann Poulard failed to clear his lines and diverted the ball into his own net.
Eden Hazard started to become more prominent as the first half wore on and the Belgian set up Dimitri Payet, but his effort was well saved by Guillermo Ochoa.
The champions got their second goal in the 37th minute as Joe Cole found space on the edge of the box before firing his shot into the back of the net.
AC Ajaccio failed to improve in the second half and Hazard was twice denied by a defiant Ochoa.
Lille's third goal didn't come until the 81st minute as Gianni Bruno headed in an accurate Hazard corner.
Hazard completed a dazzling personal display as the attacking midfielder converted a penalty for Lille's fourth following a foul by Carl Medjani.
Frederic Sammaritano scored a late consolation goal for Ajaccio with a fine finish in the 90th minute.