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.
In order to win the league a record-breaking six matches before the end of the season, Napoli have to hope closest challengers Lazio do not to win at Inter Milan in Sunday's early kick-off
Thousands of joyous Napoli supporters greeted the team early Monday as they returned from their victory over Juventus, which brought the prospect of a historic Serie A title within touching distance.
Giacomo Raspadori smashed in the stoppage time decider to claim a huge win at Juve which pushed Napoli 17 points clear at the top of the table, sweeping aside disappointment at being knocked out of the Champions League by AC Milan midweek.
Leaders Napoli were held to a goalless home draw by relegation-threatened Hellas Verona in Serie A on Saturday as Luciano Spalletti's side finished winless for the third time in their last four games in all competitions.
Ismael Bennacer gave AC Milan a slim advantage in their all-Italian Champions League quarterfinal against Napoli with the only goal in Wednesday's tight 1-0 first-leg win.
Napoli took another step closer to ending their 33-year wait to win the Serie A title after they came away from Lecce with a 2-1 win on Friday thanks to a bizarre own goal from Lecce defender Antonino Gallo.
Juventus have been ordered to close part of their stadium for their next home Serie A match against Napoli by an Italian sports judge after Inter Milan striker Romelu Lukaku was racially abused during Tuesday's Coppa Italia semi-final.
Milan have 51 points, one ahead of fourth-placed Inter Milan, and are four behind second-placed Lazio. Napoli are 20 points clear at the top
The face of a young Diego Armando Maradona gazes down from a mural in Naples' Miracles Square, watching the city gear up for a celebration it hasn't enjoyed since the Argentine soccer star was at his peak more than 30 years ago.
While the fans of Italian football continue to struggle to convince their peers from the English Premier League and LaLiga about the relevance of Serie A in European footballing hierarchy, it is with a renewed optimism that they can now boast about Napoli – the new entertainers of European football.
