Frank Anguissa and Amir Rrahmani scored Napoli's goals in an eight-minute spell in the first half before Andrea Pinamonti cut the deficit early in the second period.
Fiorentina earlier remained on Napoli's heels after their 1-0 home win over Cagliari in their first league match since midfielder Edoardo Bove's sudden collapse last weekend.
Lazio will face either Inter Milan or Udinese in the quarter-finals.
Napoli coach Antonio Conte criticised the Video Assistant Referee (VAR) for not intervening to reverse a penalty that Inter Milan's Hakan Calhanoglu eventually missed in their 1-1 draw on Sunday.
Antonio Conte's resurgent side wrapped the match up inside the first half, courtesy of an early Romelu Lukaku goal and a sensational strike by Khvicha Kvaratskhelia.
Victor Osimhen has been sidelined by Napoli after the team he fired to Serie A glory just a over year ago left him both off their squad list for the 2024/25 campaign and potentially in season-long limbo.
Belgium striker Lukaku completed a permanent move to Napoli from Chelsea on Thursday, ending a long period of limbo with the Blues.
The futures of Napoli striker Victor Osimhen and England international Ivan Toney are set to dominate the final day of the European transfer window on Friday as Chelsea continue their frenzied pursuit of new signings.
Napoli manager Antonio Conte apologised to the club's fans after his side were humbled 3-0 at Hellas Verona in Serie A on Sunday and said he took responsibility for the loss.
Napoli pull four points clear at the top of Serie A with a 5-0 hammering of Cagliari a day after champions Juventus' game in Turin was snowed off.
Maurizio Sarri warns Juventus that their days of Serie A domination were numbered as Napoli switched their focus to winning a first league title in nearly 30 years after their European exit.
Napoli coach Maurizio Sarri blasts his side's "bad attitude" in a 3-1 Europa League defeat to RB Leipzig but stresses that his team's focus this season was on the Serie A title.
Marek Hamsik equals Diego Maradona's record as Napoli's all-time top goalscorer as they took advantage of Inter Milan's first defeat of the season to move top of Serie A with a 3-1 win at Torino.
Sergio Aguero becomes Manchester City's all-time record scorer and is described as "a legend" by coach Pep Guardiola whose side booked their place in the Champions League last-16 with a 4-2 win at Napoli.
Pep Guardiola takes his swaggering Manchester City side to the home of Italian league leaders Napoli on Wednesday knowing a win will guarantee qualification for the Champions League knockout stages with two games to spare.
Manchester City beat Napoli 2-1 in their Champions League Group F match to maintain their 100 percent record after three games.
Champions Juventus and Napoli pull clear at the summit of Serie A as they continue their faultless campaigns as Inter Milan fall behind.
A Jose Callejon goal help Napoli ease into the Champions League group stage, while Sevilla also went through and Celtic suffer a scare in Kazakhstan before winning their play-off tie.
Juventus, beaten Champions League finalists twice in the past three seasons, begin the 2017-2018 season looking to extend their current record of six consecutive title wins in Italy's Serie A.
