Nicola Sansone's free-kick earned Sassuolo an historic 1-0 win over 10-man Juventus on Wednesday at the Mapei stadium.
The Sassuolo forward struck the only goal of the game in the 20th minute, a brilliant curled free-kick that left Juve goalkeeper Gianluigi Buffon rooted to the spot.
Juve had defender Giorgio Chiellini sent off for a second yellow card in the 39th minute and could not find a way past Sassuolo keeper Gianluca Pegolo.
The outcome in Sassuolo, Juve's fourth loss in Serie A, has left the defending Italian champions 12th in the standings with 12 points from 10 games.
Sassuolo, meanwhile, have kept their unbeaten run at home and have climbed to fifth position.
The visitors went into the encounter hoping to win two games in a row in the domestic competition for the first time this season.
Simone Zaza, who joined Juve from Sassuolo this summer for 18million euros, was left on the bench with Mario Mandzukic chosen to partner Paulo Dybala in Juve's attack.
Sassuolo, looking for their first ever win against Juve, were the better side. They took a 20th-minute lead when Sansone's free-kick hit the top corner for the first goal allowed by Juve in four games.
Juve almost pulled level six minutes later but Pegolo did well to keep out Paul Pogba's hard drive from 30 yards.
The visitors suffered a blow shortly after when Chiellini was handed his marching orders after a late tackle on Domenico Berardi.
Chiellini had been booked four minutes into the game for dissent.
On the stroke of half-time, Buffon kept out Sansone's bullet strike from outside the area.
Juve looked more dangerous after the restart and Pogba saw his right-footed attempt go wide early in the second half.
Leonardo Bonucci and Andrea Barzagli saw their goal-bound attempts blocked by Sassuolo defenders.
Juve coach Massimiliano Allegri brought in Alvaro Morata in place of Mandzukic on the hour.
Two minutes later and Morata fed Juan Cuadrado in the box and his right-footed shot towards the near post was saved by Pegolo.
The visitors continued to push forward but could not break Sassuolo's well-placed defence and were limited to outside shooting.
Hernanes and Mario Lemina's long-range attempts were kept out by Pegolo.
Sassuolo were fortunate not to have Francesco Acerbi sent off in the 77th minute after he elbowed Dybala in the face but the referee did not see the action.
With 12 minutes remaining, Allegri brought in Zaza in place of Dybala but Juve could not find the equaliser.