Domenico Berardi heaped more misery on Milan again as he netted a hat-trick in Sassuolo's 3-2 Serie A home win, while Cagliari's 1-0 defeat to Palermo confirmed their relegation.
The 20-year-old striker scored all four goals in the same fixture last season as Sassuolo won 4-3 and he tormented Milan again on Sunday, as the visitors ended the match with nine men.
Berardi broke the deadlock with a goal that Diego Lopez will be eager to forget, the ball squirming away from the goalkeeper before being adjudged to have crossed the line.
There was little doubt about the second as he raced away from the static Milan defence to volley past Lopez, but Giacomo Bonaventura ensured the visitors remained in the game with his fifth of the season.
Alex then drew Milan level early in the second half, but Inzaghi's side were down to 10 soon after as Bonaventura was dismissed for a second booking.
Sassuolo's man advantage paid dividends eventually as Berardi secured all three points with a close-range finish, completing a league double over Milan, who also had Suso sent off in stoppage time.
Cagliari's fate was finally sealed as they were beaten at home by mid-table Palermo.
Franco Vazquez scored the only goal of the game in the ninth minute, rendering Atalanta's 4-1 home loss to Genoa somewhat irrelevant, as Edy Reja's men secured safety as a result of Cagliari's failure to leave the coach to ponder over a "painless defeat".
Second-placed Roma survived a scare at home to lowly Udinese, coming from behind to win 2-1.
Chelsea-owned Stipe Perica put the visitors ahead with 19 minutes played, but Radja Nainggolan levelled just before the break and Vassilis Torosidis completed the turnaround in the second period, leaving Roma a point ahead of arch-rivals Lazio with two games left.
Empoli coach Maurizio Sarri was left fuming at his side's "arrogance" after they lost 2-1 at Verona despite taking a sixth-minute lead, while a Maxi Lopez double gave Torino a 2-0 victory at home to Chievo.
Thank you for reading 5 articles this month* Join now for unlimited access
Enjoy your first month for just £1 / $1 / €1
*Read 5 free articles per month without a subscription
Join now for unlimited access
Try first month for just £1 / $1 / €1
Get FourFourTwo Newsletter
The best features, fun and footballing quizzes, straight to your inbox every week.