The Azzurri had enjoyed a runaway start to their Scudetto bid, taking four wins from four under new coach Rafael Benitez to match fellow hopefuls Roma at the top of the table.
Sassuolo's experience in the top flight had been a mirror image of Napoli's, however, and they were pointless having conceded 15 goals in four games when arriving in Naples.
Simone Zaza thought he had merely given the Neroverde brief reason to cheer with his 20th-minute response to Blerim Dzemaili's early opener, but on this occasion their luck was in as Napoli ran out of steam.
While the Partenopei chased the 12th goal of a barnstorming start to the new season, Sassuolo were eager to avoid conceding a 16th in a stadium which could easily house the entire population of their hometown.
Gonzalo Higuain rattled their resolve with a shot in the fifth minute but Gianluca Pegolo punched clear.
Sassuolo then enjoyed a couple of half-chances, Zaza twisting to connect with an inswinging corner but firing over the bar before Ezequiel Schelotto's shot from distance bobbled wide.
They could do little about Napoli's opener in the 14th minute.
With the Sassuolo defence retreating, Dzemaili moved through the midfield before picking his spot and beating a stunned Pegolo from well outside the box.
The Azzurri have typically enjoyed a rush of confidence when opening the scoring this term but the blood went out of their cheeks when Sassuolo found a quick equaliser.
A move that started from deep ended with Zaza pacing into the area and the former Sampdoria striker swept the ball home under the crossbar.
Unsurprisingly Napoli were less than impressed and launched an all-out assault on the visiting goal,.
Pegolo put paid to Dries Mertens' angled drive but the keeper was at sixes and sevens when Marek Hamsik blazed a daisy-cutter towards his farcorner.
The ball swerved wide and the northerners had done enough to reach the break on a par with Benitez's men.
Napoli almost recovered the lead in the 55th minute but Federico Fernandez was two steps further away from the ball than Pegolo at a corner.
The organisation that had deserted Sassuolo in the first four games was suddenly in evidence at the San Paolo and Napoli would labour without reward for the rest of the game.
The Serie B champions could even have snatched the unlikeliest of wins, but Jasmin Kurtic's bullet header was flicked to safety by Pepe Reina as time ticked away.