Victory has all but ensured Inter of a place in next season's Europa League. For Lazio the chase is over, as they can no longer finish in the top six.
There was an emotionally charged atmosphere at the San Siro, as the Nerazzurri faithful gathered to say goodbye to Javier Zanetti. The 40-year-old was making his final home appearance for the side he's served for 19 years before retiring at the end of the season to become part of the club's staff. The Argentine had to be content with a place on the bench.
Inter made one change from last weekend's derby defeat. Zdravko Kuzmanovic came in for the suspended Esteban Cambiasso. Hernanes faced the club he left in the January transfer window.
Lazio boss Edy Reja was forced into wholesale changes. Senad Lulic was suspended, while Abdoulay Konko and Stefan Radu joined Federico Marchetti, Ederson and Helder Postiga on the sidelines. Cristian Ledesma and top scorer Antonio Candreva were only fit enough to be susbtitutes, but Miroslav Klose started his first game in a month.
Lazio took advantage of slack Inter marking to hit the front after only two minutes. Lorik Cana cushioned Bruno Pereirinha's cross and Giuseppe Biava was on hand to stab the ball in on the goalline.
The lead only lasted five minutes. Mateo Kovacic provided a defence-splitting pass for Rodrigo Palacio to toepoke past Etrit Berisha from 12 yards.
Berisha spilt a low shot from Yuto Nagatomo, but did better at smothering a shot from distance by Palacio. Midway through the first half, Felipe Anderson played in Klose and Samir Handanovic rushed out of his goal to halt the German's progress.
Keita Balde failed to see Pereirinha unmarked on the left hand side and stung Handanovic's palms from the edge of the box. The Spaniard then found space down the right flank and flashed a dangerous ball across the six yard box, but no Lazio player could put the ball into the net.
The referee was letting a lot of dangerous tackles go unpunished. He finally booked Palacio for a studs-up challenge on Pereirinha and he'll now miss Inter's final game at Chievo Verona next weekend.
Inter took the lead on 34 minutes. Kovacic split the Lazio defence again with the outside of the foot. The Croatian's inch perfect pass was tucked away by Mauro Icardi, whose first time shot found the far corner. The Argentine ran straight over to embrace Zanetti on the touchline. Palacio bagged another just three minutes later, turning in from six yards after shaking off Cana and getting on the end of Nagatomo's low cross.
Walter Mazzarri opted to keep Zanetti and the fans waiting at the start of the second half, but Lazio did introduce Ledesma. Seven minutes in, Mazzarri finally yielded and handed Zanetti his San Siro swansong. The Argentine came on with 'Zanetti 4 Ever' on his shirt and a specially commemorative armband listing every single Inter player he's shared the field with during his 19 years at the club.
Lazio refused to roll over. Handanovic needed two hands to keep out a Biava header and Keita saw an effort whistle past the goalmouth. Anderson's shot lacked the power to trouble Handanovic and Lucas Biglia volleyed inches over from 20 yards.
Diego Milito was given a round of applause from the Inter fans when he was introduced on 64 minutes. The 34-year-old is widely expected to be departing for pastures new in the summer after being relegated to a bit part player.
All the chances continued to fall to the away side. Biglia dragged wide and Keita forced Handanovic into a save at the near post. Candreva came on and he picked out an unmarked Keita, but the youngster sliced his volley into the stands.
Handanovic instinctively stuck out a leg to turn Anderson's deflected effort over the bar. The Slovenian palmed away from Candreva, then used his large frame to dive low and push out another Anderson effort.
Despite all the Lazio pressure, Inter added a fourth goal on 79 minutes. Hernanes cut inside from the right wing and curled a left footed shot into the far corner. The Brazilian refused to celebrate against his former employers.
Late on, Handanovic punched a Candreva cross clear and an unmarked Klose nodded wide. Zanetti even had time to assist security in removing an overzealous Inter fan from the field. Clearly, the emotions of the evening had become too much for some.
Players and officials from both clubs embraced Zanetti at the final whistle, ahead of a special farewell presentation for their celebrated stalwart.
Inter Milan: Handanovic; Ranocchia, Samuel, Rolando; Jonathan, (Zanetti 52) Hernanes, Kuzmanovic, (Taider 74) Kovacic, Nagatomo; Icardi, Palacio (Milito 64)
Goals: Palacio 7, 37 Icardi 34, Hernanes 79
Lazio: Berisha; Biava, Cana, Dias; Gonzalez, (Ledesma 46) Onazi, (Candreva 68) Biglia, Pereirinha; Felipe Anderson, (Minala 82) Klose, Keita
Goals: Biava 2