Stefan de Vrij had given Lazio the lead, but injuries took their toll and Napoli turned it around to win 4-1, including an incredible Dries Mertens strike.
The Aquile had been unbeaten this season between Serie A, the Europa League and Italian Super Cup.
Things seemed to be going their way when De Vrij turned in a Ciro Immobile assist from the by-line, but Bastos and Sergej Milinkovic-Savic went off injured.
Napoli took full advantage, turning the game around in under 10 minutes with a Kalidou Koulibaly tap-in from a corner, Jose Callejon strike at the end of a well-worked team move and truly ridiculous Mertens lob from a tight angle.
Lazio even went down to 10 men as Dusan Basta joined the injury list, so in stoppages Jorginho converted a penalty.
Napoli maintain their perfect start in Serie A and are joint top of the table with Juventus.
Or see how all tonight's games unfolded on the Liveblog.