Livorno, Bologna and Catania were relegated from Serie A.
Bottom side Livorno were already all but down and their fate was sealed by a 1-0 loss at home to Fiorentina, who are now guaranteed Europa League football.
Juan Cuadrado's tap in just before the hour mark decided the match, while the hosts finished with 10 men after Miguel Borja was shown a red card in stoppage time.
Catania and Bologna joined them in going down, the Sicilians' 2-1 win at the Stadio Renato Dall'Ara in vain.
Luciano Monzon's first-half opener was cancelled out by Bologna's Archimede Morleo with 10 minutes remaining, but Gonzalo Bergessio grabbed a late winner.
Results elsewhere condemned both sides to the drop, with Chievo triumphing 1-0 at Cagliari and Sassuolo winning 4-2 against Genoa.
Dario Dainelli's second-half winner saved Chievo, while Sassuolo completed a great escape thanks to late strikes from Nicola Sansone and Antonio Floro Flores, his second of the game.
Sassuolo had twice been pegged back, Emanuele Calaio and Alberto Gilardino responding to goals from Floro Flores and Davide Biondini, but they dug deep to get over the line.
Champions Juventus moved on to 99 points for the season with a 1-0 win at Roma, substitute Dani Osvaldo with the goal in the fourth minute of second-half stoppage time.
Torino's 1-1 draw at home to Parma ensured the fight for the final Europa League place would go down to the final day of the season.
Torino remained a point ahead of their opponents and took the lead through Italy's leading scorer Ciro Immobile just before the break
They received another boost when Alessandro Lucarelli was sent off in the 63rd minute, but Jonathan Biabiany brought the 10 men level after Antonio Cassano's penalty was saved.
Immobile also saw red for diving late on.
Milan suffered a setback in their bid to qualify for the Europa League as they fell to a last-gasp 2-1 defeat to local rivals Atalanta.
An own goal from Gianpaolo Bellini gave the Rossoneri the lead early in the second half, but a second-half penalty from German Denis and a Franco Brienza effort with the last kick of the game turned the match on its head.
The defeat left Milan two points behind Torino.
Finally, Napoli thumped Sampdoria 5-2.
Duvan Zapata put the visitors in front before Lorenzo Insigne made it two. Eder pulled a goal back for the Blucerchiati, but Jose Callejon soon restored Napoli's two-goal advantage.
Marek Hamsik and an own goal from Shkodran Mustafi gave the Azzurri a comfortable lead before Pawel Wszolek grabbed a late consolation.