On a day that saw 25 goals across the seven matches in Italy's top flight, Walter Mazzarri's side topped the scoring ranks with an emphatic 7-0 home victory.
The result comes almost exactly 12 months after Inter hammered Sassuolo by the same scoreline on the road last season.
Mauro Icardi began the onslaught in the fourth minute with the game's opening goal and went on to record a hat-trick by the 53rd minute.
Mateo Kovacic, Pablo Daniel Osvaldo (two) and Fredy Guarin also found the target, while Domenico Berardi was sent off for the beleaguered visitors, as Inter shrugged off the disappointment of their opening-game stalemate with Torino.
Meanwhile, city neighbours Milan edged a nine-goal thriller 5-4 against Roberto Donadoni's Parma.
Filippo Inzaghi's side looked to be in complete control going into the break 3-1 ahead but Parma never gave in and scored early in the second half through Felipe.
The goals continued to flow as Nigel de Jong and Jeremy Menez, with an audacious back heel, netted for the visitors and Alessandro Lucarelli scored Parma's third.
Both sides ended with 10 men after Daniele Bonera and Felipe were dismissed and the game's final piece of action saw Diego Lopez misjudge a Mattia De Sciglio backpass to conceded a farcical own goal.
Napoli were surprised at the Stadio San Paolo as Chievo took all three points with a 1-0 win on a frustrating day for Rafael Benitez's side.
Gonzalo Higuain saw a first-half penalty saved but the hosts continued to drive forward and finished the match with 33 attempts on goal, a club record in a single Serie A match since 2004-05.
However, it was Maxi Lopez who broke the deadlock for the visitors four minutes after the break and they held on despite intense pressure from the hosts to claim all three points.
Things were much easier for Sampdoria as they beat Torino 2-0 thanks to goals from Manolo Gabbiadini and Stefano Okaka.
Having peppered the Torino goal the hosts had to wait until the 34th minute to open the scoring as Gabbiadini registered his first league strike since March.
Striker Okaka doubled the lead in the 79th minute as he carried the ball through the Torino half before firing home from inside the penalty area.
Elsewhere, Atalanta won 2-1 at Cagliari, Lazio overcame Cesena 3-0, and Fiorentina were held 0-0 by Genoa despite the visitors having Facundo Roncaglia dismissed.