The Partenopei remain unbeaten in the Italian top flight after 13 matches, dropping points just twice all term as they seek a first title in 28 years.
This latest victory, secured through a goal in either half from Lorenzo Insigne and Piotr Zielinski, increases the pressure on visiting boss Vincenzo Montella as Milan remain out of the top-four picture.
Napoli, who were held to a surprise goalless draw at Chievo prior to the international break, came close to making a breakthrough 13 minutes in when Gianluigi Donnarumma produced a good save to deny Jose Callejon from a few yards out.
The breakthrough goal arrived soon after as Insigne converted after racing on to Jorginho's through-ball - his sixth goal in 10 matches against Milan - but it was only awarded following confirmation from VAR that the Italian attacker was indeed onside.
Insigne was denied a second by the frame of the goal before the interval, before Donnarumma again came to the rescue to keep out the same player.
Milan did begin to see more of the ball, but it was all in vain as Napoli scored a second via substitute Zielinski, who rounded off a fine team move by tucking the ball through Donnarumma's legs.
Giacomo Bonaventura finally managed a serious shot on goal for the visitors 76 minutes in, which Reina was equal to, and Alessio Romagnoli went one better by finding the net with a smart volley in added time.
Milan could not find a leveller against the run of play, though, meaning that they have now failed to beat Napoli in six successive matches and find themselves down in seventh place.