Napoli hit the woodwork three times, but eventually squeezed past 10-man Lazio with Arkadiusz Milik and Jose Callejon goals.
The Partenopei had to do without suspended Kalidou Koulibaly, Lorenzo Insigne and Allan, plus injured Marek Hamsik, but Dries Mertens and Raul Albiol shook off problems to start. The Biancocelesti had Adam Marusic banned and Valon Berisha side-lined, so Senad Lulic moved to the right with Jordan Lukaku getting his first Serie A start of the season.
Lazio have now managed just one point in their last eight meetings with Napoli, since a dramatic 4-2 victory here in May 2015 that decided Champions League qualification, complete with missed Gonzalo Higuain penalty.
There were concerns on how Napoli would defend aerial threats without Koulibaly and that immediately became apparent after four minutes when Alex Meret had his gloves stung by a Sergej Milinkovic-Savic header at the back post.
Arkadiusz Milik went even closer, his ferocious volley from a Mario Rui cross smashing into the top of the upright from 12 yards, rattling the frame of the goal.
Incredibly, Milik was denied by the woodwork again, this time his diving header on a Piotr Zielinski flicked assist was fingertipped on to the post by Thomas Strakosha.
Meret flew to palm away another Milinkovic-Savic strike, but Lazio lost Luiz Felipe to injury. It was his replacement, Bastos, who was out of position for the Napoli goal when the play was spread from left to right until Jose Callejon drilled into the far bottom corner. It was his first Serie A goal of the season and confirmed Lazio as his favourite victims, as it was his sixth against them.
It was third time lucky for Milik, who after hitting the woodwork twice, found the near top corner with a sensational left-footed free kick to double Napoli’s lead.
Joaquin Correa replaced Jordan Lukaku for the second half, as Lazio had to go all-attack to recover from the 2-0 deficit. He made an immediate impact, testing Meret at the near post and seeing his glancing header flash just wide.
Lazio were building momentum, but Napoli almost scored on the counter, this time Fabian Ruiz rattling the frame of the goal with a powerful strike and Strakosha with a one-handed save on the Milik follow-up.
Moments later, Meret used his legs to parry a Ciro Immobile volley at the back stick, while another Callejon effort off the bar wouldn’t have counted anyway because he was offside.
The goal had been coming and Immobile scored it, stroking his finish between Albiol’s legs into the far bottom corner. It was the native Neapolitan’s first ever goal at the Stadio San Paolo.
Just as Lazio were pouring forward, Milinkovic-Savic misplaced a back-pass and Acerbi had to at least attempt the tackle. It was a second yellow card and the defender was sent off, meaning he’ll be suspended next week against Juventus and more importantly cannot beat Javier Zanetti’s record of 162 competitive games in a row. Acerbi’s run ends at 148 complete matches, this would’ve been his 149th if he had made it to the final whistle.
It remained open with chances at both ends, as Bastos fired over and Adam Ounas saw his acrobatic volley parried by Strakosha.
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Sent off: Acerbi 70 (L)