Napoli travelled to San Siro on the back of a confidence-boosting 2-1 win over Borussia Dortmund in the UEFA Champions League on Wednesday, but they showed no signs of a continental hangover by leaving Milan with all three points.
Miguel Britos put Napoli ahead in the sixth minute, with Gonzalo Higuain adding the second after the break.
Mario Balotelli failed to score a penalty for the first time in his professional career as Pepe Reina denied him, and although the Italian did get a goal in spectacular style late on, Rafael Benitez’s side held on to the win.
The defeat was compounded for Milan after the final whistle when Balotelli was shown a red card, with his dismissal appearing to be for dissent.
One of Italy's most famous fixtures also took place on Sunday as Roma and Lazio contested the Rome derby at Stadio Olimpico.
Rudi Garcia's side had begun the season in impressive form with three wins from three, and although the score was level at the break, they were well on their way to three points in the second half when Federico Balzaretti volleyed them into the lead after excellent play by Francesco Totti on the byline.
Lazio's cause was not helped by Andre Dias being shown a straight red card eight minutes from time.
Adem Ljajic compounded Lazio's misery by converting a penalty in stoppage time, moving them on to a maximum 12 points.
Inter's resurgence following a torrid campaign last year continued against Sassuolo, as they ran riot against the promoted side to win 7-0 away from home.
Rodrigo Palacio broke the deadlock early on with his third goal of the season before Spahir Taider and a Raffaele Pucino own goal ensured a 3-0 lead at the break.
Ricky Alvarez added a fourth before his Argentinian compatriots Esteban Cambiasso and Diego Milito completed the rout, with the latter scoring twice on his return from injury.
Reigning champions Juventus got back to winning ways following a week which included draws against Inter and Copenhagen.
Hellas Verona were their victims in Turin, although the visitors opened the scoring as Fabrizio Cacciatore tapped in from close range.
A brilliant finish across goal from Carlos Tevez followed by a Fernando Llorente header on his home debut did enough to claim the three points for Antonio Conte’s side as they won 2-1, but it could have been far more comfortable.
Fiorentina remained in the top three thanks to a 2-0 win at Atalanta, the hosts' third defeat of the season.
Meanwhile, Torino made a significant move up the table thanks to a 2-1 triumph at Bologna, while Parma and Catania remain in the bottom three after their 0-0 draw.
