Brazilian midfielder Allan opened the scoring midway through the first half for Maurizio Sarri's side before Diego Falcinelli scored an undeserved equaliser in the 41st minute.
Napoli's advantage was restored on the stroke of half-time as goalkeeper Andrea Consigli parried a corner into his own net to concede a goal that was attributed to Jose Callejon, before Dries Mertens ensured a 10th win in 11 league games with a second-half strike.
Inter Milan can move second and close the leaders' advantage to two points if they win against Hellas Verona on Monday evening (Tuesday morning AEDT), but it is the Partenopei who are setting a blistering early pace in the race for the Scudetto.
The visitors almost took a shock lead after just 11 minutes, but Stefano Sensi's whipped free-kick from the edge of the penalty area crashed back off Jose Reina's crossbar.
Sensi then played an unfortunate role in Napoli's opener in the 22nd minute. The midfielder took too long to clear on the edge of his own area and had his pocket picked by Allan, who coolly slotted through the legs of Consigli.
Faouzi Ghoulam came agonisingly close to extending the hosts' lead shortly after, thumping a half volley against the post after a corner fell kindly to him.
Sassuolo responded well to the setback and scored an unlikely leveller four minutes before the break. Matteo Politano delivered a teasing cross from the right and Falcinelli beat his marker to plant a firm header past Reina for his first goal of the season.
Their joy was short-lived, though, as Consigli conspired to punch Lorenzo Insigne's corner, which had glanced off the head of Callejon, into this own net just a minute before half-time to restore Napoli's lead.
Mertens's stunning form continued nine minutes into the second half as he bundled home Raul Albiol's knockdown for his 10th league goal of the campaign.
Francesco Cassata thumped a header against the post as Sassuolo tried in vain to find a way back into the game, while substitute Piotr Zielinski was denied a fourth late on for Sarri's side as his long-range effort hit both posts before being scooped up by Consigli, who also saw an injury-time strike from Mertens flash narrowly wide.
Key Opta stats:
- Dries Mertens played his 200th game for Napoli in all competitions (80 goals).
- The Belgium international has found the net in each of the last two Serie A clashes against Sassuolo.
- Diego Falcinelli took 19 shots to score his first goal in Serie A this season.
- Just four of Callejon's 52 Serie A goals have come from outside the box.
- Napoli have not lost any of their first 11 Serie A match-days of the season for the first time since 1989-1990, when they won the Scudetto.
- Sassuolo have set a new negative record of points taken after 11 match-days, eight – they picked up nine in their very first season in the top flight.