Juventus had won eight games in a row without conceding, but that record was mercilessly snapped at the Diego Armando Maradona Stadium.
Viktor Osymkhen scored twice, as well as Khvica Kvaratshelia, Amir Rahmani and Elif Elmas.
Angel Di Maria replied for Juventus, who eventually dropped to third place.
Osimen opened the scoring for Napoli before passing to Quaratzhelia to double the lead, but Di Maria made the save before half-time.
Rahmani restored the home side’s two-goal lead 10 minutes after the break and from there Luciano Spalletti’s side started rampant.
Georgian star Kvaratskhelia beat Osimhen with a superb cross and the Nigerian striker headed in his 12th Serie A goal of the season.
Elmas’ deflected strike completed the scoring as Juventus conceded five goals in a competitive game for the first time since May 1993.
Massimiliano Allegri’s side have conceded just seven in the top flight this season and sit third, level on points with second-placed AC Milan.
But it was a thrilling performance from Napoli that underlines the hosts’ advantage for a first Serie A title since Maradona was in their ranks 33 years ago.
