As a result, Inter and city rival AC Milan are tied for first place in the standings on points after American star Christian Pulisic helped the Rossoneri defeat Cagliari 3-1.
Wednesday's unexpected 2-1 loss to Sassuolo at home put an end to Inter Milan's undefeated start to the Serie A season.
Denzel Dumfries gave Inter the lead just before halftime, but Sassuolo responded with two goals in nine second-half minutes, including a stunning goal from Domenico Berardi. This follows Sassuolo's 4-2 triumph over Juventus over the weekend.
The outcome saw Inter draw even with city rival AC Milan at the top of the standings as American international Christian Pulisic assisted the Rossoneri to a 3-1 victory over Cagliari.
Inter, the only remaining unbeaten team in Serie A, was aiming to extend its excellent start to the season to six victories in as many games.
When it gained the lead in the first half stoppages, everything seemed to be going according to plan. Right before shooting between the legs of another defender and into the bottom left corner, Dumfries darted inside from the right and confused one defender.
When Berardi found Nedim Bajrami, Sassuolo equalised in the 54th minute when Bajrami's strike slid between Inter custodian Yann Sommer and his near post. However, the warning signs had been there.
OSIMHEN CHEERED
Victor Osimhen put his off-the-field troubles behind him by scoring in Napoli's 4-1 victory over Udinese.
Near the end of the first half, the 24-year-old Osimhen scored Napoli's second goal of the game with a pinpoint shot into the far bottom corner.
Osimhen, who had encouragement from the crowd before to the game, is thinking about suing his club after it released a video at the weekend mocking his missed penalty.
In the 19th minute of play on Wednesday, Napoli received another penalty. Piotr Zieliski took the shot and made the conversion this time.
After Lazar Samardi had given Udinese the lead, Khvicha Kvaratskhelia scored his first goal of the season in the second half, and Giovanni Simeone added another for Napoli.
NEW SIGNINGS GLAMOROUS
As the newcomers assumed leadership, Pulisic assisted both of the first-time Serie A goal scorers, Noah Okafor and Ruben Loftus-Cheek.
Cagliari unexpectedly took the lead in the 29th minute thanks to Zito Luvumbo, but Milan came back just before halftime.
After Pulisic had eluded his defender and brought the ball back from the byline, Cagliari custodian Boris Radunovi made a terrible mistake with the ball, allowing Okafor to tap in the rebound in the 40th minute.
Fikayo Tomori scored a goal from close range to give the Rossoneri the lead on the stroke of halftime despite Radunovi's best efforts to save a cross from Tijjani Reijnders, another summer signing for Milan.
Ahead by more than an hour, Milan. The ball from Pulisic's blocked cross bounced back to him, and he cut it back to the outside of the box for Loftus-Cheek, a former teammate at Chelsea, to slam into the bottom left corner.
OUT OF BASE
Empoli, a newly promoted team, defeated Salernitana 1-0 thanks to a goal from Tommaso Baldanzi, giving it its first points back in Serie A.
Empoli became the first team in Serie A history to finish the first five rounds without a point or a goal.
Lazio defeated Torino 2-0, and Atalanta triumphed 1-0 at Hellas Verona.