Sampdoria were haunted by ex-player Mauro Icardi, who scored twice in Inter's 4-0 victory at Stadio Comunale Luigi Ferraris.
In a match that saw coaches Walter Mazzarri and Sinisa Mihajlovic face their former clubs, Icardi also came face-to-face with Maxi Lopez amid a much-publicised spat between the two, centred around the relationship between Icardi and Lopez's ex-wife.
Icardi broke the deadlock in an ill-tempered first half, which saw Lopez miss a penalty, before Sampdoria were reduced to 10 men when Eder - initially booked for simulation - was handed another caution for his part in a melee that included an altercation between him and Inter goalkeeper Samir Handanovic.
Inter took control of the match in the second half, with Walter Samuel making it 2-0 on the hour-mark, and there was still time for Icardi and Rodrigo Palacio to add to their lead as they moved fifth in the table.
While Inter occupy the last guaranteed UEFA Europa League spot, sixth place could also provide a berth in Europe's secondary competition should Coppa Italia finalists Napoli and Fiorentina finish in the top five.
Parma sit sixth currently, but their 1-1 draw at relegation-threatened Bologna allowed the chasing pack to gain ground.
They had Raffaele Palladino to thank for even getting a point, with the attacker equalising in the 79th minute.
Milan were one of the sides to move closer to Parma as their 1-0 win against rock-bottom Catania signalled a fourth straight league success for the first time since March 2013.
Riccardo Montolivo's long-range drive in the first half was the difference between the two sides as the visitors - who are now eight points adrift of safety - were unable to provide new coach Maurizio Pellegrino with a point on his second debut in charge of the club.
Catania had Fabian Rinaudo sent off in the closing stages.
Torino climbed to seventh after a last-gasp 2-1 home win over Genoa at Stadio Olimpico.
Alberto Gilardino thought he had given the visitors all three points with an 85th-minute effort, but goals deep into injury time from Ciro Immobile and Alessio Cerci gave Torino an incredible win.
Lazio's European hopes suffered a blow as Gonzalo Higuain's hat-trick for third-placed Napoli saw them record a 4-2 win, while Verona and Fiorentina played out an eight-goal thriller.
Alberto Aquilani scored twice for Fiorentina in their 5-3 triumph, while Juan Cuadrado, Borja Valero and Alessandro Matri also netted for the victors.
Verona ended the game with 10 men after Marco Donadel was sent off with 21 minutes left.
The day's other match saw Alberto Paloschi score a hat-trick as Chievo won 4-2 at Livorno.
