A goal and three assists from Italy international Domenico Berardi piled on the misery for Milan as Sassuolo thrashed the Rossoneri 5-2 at San Siro.
Sassuolo took an early two-goal lead thanks to goals from Gregoire Defrel and Davide Frattesi prior to Olivier Giroud pulling one back for the hosts.
Berardi made it 3-1 after just 30 minutes before Armand Lauriente's penalty and Matheus Henrique's effort in the second half handed Milan their second chastening loss in a week after their 4-0 humbling at Lazio on Tuesday.
Divock Origi scored a consolation for Stefano Pioli's side, who are now six games without a win heading into next weekend's Milan derby, including four in Serie A as their title defence continues to falter.
A VAR review denied Giroud an eighth-minute opener and, to make matters significantly worse, Milan found themselves two down inside 22 minutes.
Berardi squared for Defrel to tap in the opener before the same man fed Frattesi, who fired past Ciprian Tatarusanu at his near post after great work in the area.
Milan provided a swift response when Giroud expertly headed Davide Calabria's cross into the far corner in the 25th minute.
But the two-goal lead was restored on the half-hour mark when Berardi flicked a near-post header past Tatarusanu from a corner.
Milan's hopes of a second-half comeback were doused almost immediately as Lauriente was brought down in the penalty area by Calabria after 33 seconds of the restart, allowing the Frenchman to make it 4-1 from the spot, meaning Milan had conceded at least four goals in back-to-back Serie A games for the first time in their history.
Ante Rebic had a goal ruled out for offside before Henrique fired in a fifth with just over 10 minutes remaining, with Origi's curling strike into the top corner doing little to lift the gloom among the home fans.