Goals from Giovanni Di Lorenzo, Khvicha Kvaratskhelia, Romelu Lukaku and Alessandro Buongiorno gave Napoli their third straight win and a one-point lead over Inter, Torino and Juventus, who they face in Turin next weekend.
Sunday's display was another step in the right direction for new coach Antonio Conte, who is already having to field questions about whether his team will challenge for the league title.
"Teams are still settling in as the transfer window closed late and we are all trying to find our shape," said Conte to DAZN.
"We've worked hard over the last two and a half months, we've got to keep pushing forward without thinking about anyone else."
Napoli's win was marred by ugly scenes midway through the opening period when the away fans unveiled a banner which mimicked sheep bleating and sparked the throwing of objects between the two sets of supporters.
That banner came after Napoli's fans were pictured with another one on their ferry trip to largely rural Sardinia which read "sheep hunting".
The match was stopped for seven minutes as both home and away ends supporters threw projectiles and flares.
Antonio Conte's side were already leading at that point through Di Lorenzo's wildly deflected 18th-minute opener, and Kvaratskhelia and Lukaku showed signs of a burgeoning partnership by setting each other up for the goals which sealed the three points by the 70th minute.
Buongiorno nodded home the fourth in stoppage time to make it a perfect night for Napoli and set up a mouth-watering clash with Juve.
Inter gave up their league lead as Denzel Dumfries saved a point for the champions with three minutes remaining after Dany Mota's brilliant 81st minute header threatened to give Monza their first win under new coach Alessandro Nesta.
Simone Inzaghi's unbeaten side, who would have moved a point above Napoli with a win, were uninspiring in a largely drab encounter at the U-Power Stadium and will need to improve at City on Wednesday night, with the Milan derby also coming up next weekend.
"We created some chances but weren't able to take advantage. We were slower and not as on it as we normally are," said Inzaghi to DAZN.
Lookman back with bang
Ademola Lookman made sure that Atalanta warmed up for their return to the Champions League with the winner in a 3-2 victory over Fiorentina.
Nigeria forward Lookman did not feature in Atalanta's first three league matches after agitating for a transfer to Paris Saint-Germain.
But the 26-year-old netted the decisive strike in stoppage time at the end of the first half, jinking through the Fiorentina defence before shooting past David de Gea, seconds after Charles De Ketelaere headed Atalanta level.
Lookman, the hat-trick hero from last season's Europa League final triumph, also floated in a pinpoint cross for Mateo Retegui to head in Atalanta's first equaliser in the 21st minute.
His immediate impact is great news for coach Gian Piero Gasperini, whose side host Arsenal on Thursday night and entertained their home fans in the newly-completed Gewiss Stadium.
"We're very pleased to be playing in the Champions league this season," added Lookman.
"We deserve it so we have to demonstrate that again on Thursday with the same drive, the same mentality that we showed today."
Atalanta, whose most recent appearance in the Champions League was in 2021, played their first three Serie A fixtures away from Bergamo to allow the club to put the finishing touches to their redeveloped home.
They are eighth on six points, three ahead of 14th-placed Fiorentina who twice went ahead in the first half through Lucas Martinez Quarta and Moise Kean but are yet to win under new coach Raffaele Palladino.
Earlier Genoa snatched a 1-1 home draw with Roma in the final seconds to continue their positive start to the season.
