Antonio Conte's team are three points ahead of Atalanta thanks to a superb individual goal from David Neres in the 29th minute, Romelu Lukaku's penalty not long after half-time and a cool Scott McTominay finish in the 68th minute.
Saturday's win in Florence was Napoli's fourth in a row in Italy's top flight and further strengthened their claim for a fourth league crown after their disastrous Scudetto defence last season.
"We're proud of what we're doing, having 44 points after 19 matches wouldn't have been imaginable at the start of the season," said Conte's assistant Cristian Stellini to DAZN.
However Napoli have played a game more than Atalanta and two more than reigning champions Inter Milan, with that pair missing league action this weekend due to the Super Cup.
Inter, who trail Napoli by four points, will face local rivals AC Milan in the Super Cup final in Saudi Arabia on Monday after beating Atalanta in the semis.
Atalanta will play their match from this round of fixtures when they host Juventus on January 14, with Bologna visiting Inter the following day.
Fiorentina are sixth and 12 points off the title pace after a third defeat in four matches.
The hosts were angered by Moise Kean having a fine goal ruled out for handball moments after Neres slalomed through the Fiorentina defence and slammed his finish past David de Gea.
Neres started in an unusual Napoli front three which also featured full-back Leonardo Spinazzola due to injuries to Matteo Politano and Khvicha Kvaratskhelia.
"They deserved to win, they were far more clinical than us and punished us for every little mistake," said Fiorentina coach Raffaele Palladino.
Earlier Venezia stayed second-from-bottom after being held to a 1-1 home draw by Empoli, while fellow strugglers Verona attempt to pull away from the relegation zone against Udinese.
