The Brazilian striker's debut did not disappoint, although it was his compatriot Ronaldo's first two goals of the season which ended Napoli's challenge.
He opened the scoring in the 16th minute, but the visitors reacted well and Roberto Sosa grabbed an equaliser in the 28th minute.
Clarence Seedorf restored Milan's lead three minutes later, but a penalty from Maurizio Domizzi saw Napoli go in at the break on level terms before the home side ran rampage in the second half.
Ronaldo and Kaka put the result beyond doubt before Pato added the icing in the 74th minute with his first goal for the Rossoneri.
Napoli's miserable evening was completed with the dismissal of Walter Gargano.
Pato, a 22 million euro signing last summer, was finally eligible to play his first game for the club and the anticipation was unrivalled.
The man rated by Milan coach Carlo Ancelotti as better than Ronaldinho, and tipped by World Player of the Year and team-mate Kaka to emulate his own success at the club, was who most inside the San Siro had bought a ticket to see.
And they were not disappointed, even if it was another Brazilian who eventually stole the show.
Ronaldo was absent due to injury for the first four months of the season but, after flirting with a transfer to Flamengo, has proved his heart is still with Milan.
He opened the scoring after 16 minutes with a shot which looped off the feet of Napoli goalkeeper Gennaro Iezzo and into the net.
Andrea Cupi thought his brave effort had cleared the ball from underneath his own crossbar but the ball was judged to have crossed the line.
However, Napoli were not downbeat and they played the ball around confidently with the lively Ezequiel Lavezzi a constant threat.
His perfectly-weighted volley handed Sosa a gilt-edged opportunity to equalise, and he duly obliged with a one-touch finish in front of Dida.
Just three minutes later though, Pato twice went close to a debut goal.
His second effort rebounded to Seedorf, who took no hesitation in volleying into the roof of the net.
Pato followed suit with a volley of his own 10 minutes before the break, but Iezzo made an excellent save.
The visitors were back on level terms in the 38th minute when a rash challenge by Kakha Kaladze on Lavezzi earned them a penalty, which Domizzi converted.
They reached the halfway stage of the game on par with Milan, but a whirlwind second half by the home team blew them away.
The visitors were sent toppling just 30 seconds after the restart when Ronaldo nodded Seedorf's cross in from six yards.
And an unstoppable shot from Kaka in the 68th minute put the result beyond doubt.
Pato then added his name to the scoresheet 15 minutes from time. The Brazilian wonderkid brought a long ball down excellently before breezing past Domizzi and firing home from 10 yards out.
He almost grabbed a second three minutes later, beating Domizzi once again, but shooting too close to Iezzo at his near post.
Perhaps a second goal would have been too much to ask for, but he troubled the Napoli defence all night.
Gargano certainly had enough of him as he earned a second yellow card in the final minute for a tackle on the 18-year-old which was born of frustration.
