The defending champions had not won at the San Paolo since 2000 prior to Sunday's clash, but ended that wait with a clinical performance.
Paul Pogba put Juve ahead with a stunning volley in the 29th minute, yet Miguel Britos levelled matters for Napoli, who won the Suppercoppa Italiana encounter between the two last month, converting Dries Mertens corner in the 64th minute.
However, Martin Caceres turned in Andrea Pirlo's free-kick to give Juve the lead once more in his first game since October and Arturo Vidal wrapped up the points with an emphatic finish at the end of a rapid Juve counter.
Victory for Juve puts them in control at the summit after Francesco Totti salvaged a 2-2 draw for Roma in their derby with Lazio.
Lazio, who adorned their shirts with 'Je Suis Charlie' in a show of solidarity with the victims of the Charlie Hebdo shootings in Paris, took the lead in the 22nd minute through captain Stefano Mauri.
Mauri volleyed home Felipe Anderson's chipped pass, and then returned the favour as his backheel was tucked away by the Brazilian with a deflected low drive.
But the 38-year-old Totti sparked a fightback, slotting Kevin Strootman's ball beyond Federico Marchetti in the 48th minute before brilliantly converting a far-post cross from Jose Holebas to restore parity.
Totti celebrated his second with a 'selfie' in front of the celebrating Roma fans, however, Rudi Garcia's side could not complete a dramatic turnaround.
Inter made it four league games unbeaten as they beat Genoa 3-1 to secure Roberto Mancini's first Serie A win at San Siro since taking over for a second time in November.
Former Genoa man Rodrigo Palacio put Inter ahead with a close-range finish and Mauro Icardi doubled the hosts' lead with a header from Hernanes' corner.
Armando Izzo gave Genoa hope five minutes from time, only for Nemanja Vidic to settle the contest in Inter's favour three minutes later.
Fiorentina were victorious in the day's most goal-laden encounter, Vincenzo Montella's men winning a 4-3 thriller versus Palermo.
Juan Cuadrado and Joaquin made sure of the points for Fiorentina after goals from Manuel Pasqual and Jose Basanta had been cancelled out by a Robin Quaison double.
Parma's dreadful season continued with a 3-1 loss at Verona, Gianfranco Zola claimed his first win as Cagliari coach with a 2-1 triumph over Cesena, and Sampdoria beat Empoli 1-0.
Elsewhere, a 90th-minute goal from Dejan Lazarevic earned Chievo a 1-1 draw at 10-man Atalanta, who had Gianpaolo Bellini sent off a minute earlier.
