Monaco enjoyed plenty of early possession, but they were unable to break the deadlock until the 52nd minute when Berbatov headed home Moutinho's corner.
The Bulgarian striker doubled their lead with 16 minutes remaining when he latched onto James Rodriguez's through-ball to tuck the ball past Guillermo Ochoa.
Ajaccio gave themselves hope with as they instantly pulled a goal back through Junior Tallo.
However, that hope was extinguished when Geoffrey Kondogbia received Berbatov's pass before finding the bottom corner of the net.
In stoppage time, Claudio Ranieri's side added a fourth through Lucos Ocampos and the result maintains some pressure on Paris Saint-Germain, although a seven-point deficit to the league leaders almost certainly means they will settle for second place in Ligue 1.