The contest pitted the top two in the table against each other, as well as Napoli's league-best attack against Juventus' league-best defence, but there was only one winner on the night as the leaders ran riot to knock Juventus down to third on goal difference.
Victor Osimhen scored twice and also helped himself to an assist in a man-of-the-match display, although Khvicha Kvaratskhelia was also instrumental in the victory with two assists and a goal of his own.
At least one of the pair had a hand in each of the first four goals on the night, before Elif Elmas capped off the rout 18 minutes from time.
The result adds to Napoli's growing list of impressive scorelines so far this season and will go down as one of their greatest-ever victories over their bitter rivals.
Indeed, it is only the second time that they have ever scored five goals against Juventus, also doing so during their previous Diego Maradona-inspired heyday in 1988, while it is the first time that Juventus have shipped five goals in any Serie A game since 1993.
The result was made all the more remarkable given that Massimiliano Allegri's side had not conceded in any of their previous eight Serie A games heading into the match, a run of clean sheets that stretched back to October and was their fifth-longest such streak ever.
It took Osimhen just 14 minutes to break that resolve on the night, nodding home after Wojciech Szczesny had denied Kvaratskhelia's acrobatic effort - the first league goal Juve had conceded in 770 minutes of action.
Osimhen then unselfishly squared for Kvaratskhelia to double the lead after 39 minutes, although Juve quickly responded through Angel Di Maria, who had earlier hit the woodwork too.
While the visitors may have felt that they were well in the game at half time, a fine strike from Amir Rrahmani 10 minutes after the restart, followed by Osimhen's second 10 minutes after that, put Napoli in complete control of the contest.
Elmas's deflected strike just seven minutes later piled even more misery on Juventus, who saw their eight-game winning streak - which had catapulted them back into title contention after a poor start to the season - ended in humiliating fashion.
The result is another major boost to Napoli's hopes of winning the Serie A title for the first time since 1990 and only the third time overall, whereas Juventus could now end the weekend as low as fourth depending on results elsewhere.