Walter Mazzarri's men inflicted a resounding drubbing over the newly promoted outfit, and Diego Milito netted twice in his return from a long-term injury bout.
Walter Mazzarri's side was dominant from start to finish, with Rodrigo Palacio setting the tone in the seventh minute with the game's first goal.
Saphir Taider's strike and a Raffaele Pucino own goal gave Inter a 3-0 lead at the break before Diego Milito struck twice in the second half, and Ricky Alvarez and Esteban Cambiasso also scored.
Milito's first goal was widely celebrated, with the Argentine netting in his comeback appearance after a serious knee injury. The 34-year-old Milito, who had not played for Inter in more than seven months, came off the bench in the second half and produced a smart finish before Cambiasso added a 20-yard strike.
And there was still time for Milito to grab a second, as he tapped in Fredy Guarin's assist to cap off a sensational victory.
Inter's position at the top of the table may only last a matter of hours, but the club's fans will enjoy it, having endured a disappointing campaign last season, in which their side finished ninth.
Mazzarri's new-look Inter has conceded just one goal in five competitive matches this season while scoring 17 goals.
The Nerazzurri were unchanged from the team that drew 1-1 with Juventus last week, while rock-bottom Sassuolo, which had lost all three of its Serie A fixtures this season, shuffled the pack.
The last-place side made three changes, including the recall of former Udinese striker Antonio Floro Flores, but it did no good, as Inter went ahead inside the first 10 minutes.
After a spell of Inter pressure that saw the visitors win multiple early corners, Japan international Yuto Nagatomo burst down the left flank before producing a superb cross for Palacio to tap in.
Jonathan had an effort well blocked for Inter as it pressed for a second, before Algerian Taider found himself in the right place at the right time. He followed in a saved Palacio effort to score easily past Alberto Pomini, and the goals kept on coming for the visitors.
Their third, scored in the 33rd minute, made a mockery of Sassuolo's defense, as a long ball from the terrific Guarin bounced in between Jonathan Rossini and Pucino.
With Haider lurking, Pucino panicked and steered a header over a stranded Pomini as Inter's traveling fans celebrated again.
Jonathan almost scored a fourth for Inter, but his effort was well saved, while Floro Flores had two opportunities before the break, the second of which forced a smart stop from Samir Handanovic.
Alvarez was also a constant threat for Inter, and after going close early in the second half, he got himself on the scoresheet, tapping in another rebound from a Palacio shot, before Milito enjoyed his moment in the sun in the 64th minute.
Alvarez was the provider, getting to the end line before cutting back for Milito. Cambiasso got in on the act with 15 minutes remaining, scoring an excellent curling finish on his left foot.
Milito wrapped up the win with an easy second, seven minutes from time, as Inter scored more than six goals in a league match for the first time since 1996.