A subdued affair in Belgrade saw Palacio prove to be the catalyst for the second time against the Serbians, with his Colombian teammate also getting on the scoresheet
Andrea Stramaccioni's side failed to hit the heights of its Derby d'Italia scalp over Juventus, and it needed Rodrigo Palacio to step to the plate with two goals midway through the second half, before Fredy Guarin could round off the victory in the latter stages. Nemanja Tomic also netted late on but it proved to be scant consolation for the hosts.
The opening passages saw the hosts looking the better side, as they looked to make home advantage count against the Nerazzurri, but coach Vladimir Vermezovic would have been dispirited to see his side fail to translate its possession into chances.
On the other hand, the energy of Alvaro Pereira initially appeared to be Inter's most threatening outlets, but the team struggled to muster any fluency in its play. However, it soon began to take control of the tie.
Inter's improvement could have been halted by a surprise Partizan goal straight after the interval but Samir Handanovic was on red alert to pull off an instinctive stop from Juan Jesus' botched clearance on the end of a Serbian cross.
Yet the Italians used the scare as motivation for a subsequent goal rush. Moments later, Guarin played his way into the box and rolled a low ball across goal for Palacio to finish with a simple tap-in.
Milan Smjlancic then tried his best to put Partizan back on level terms, but Handanovic again came to the rescue, extending an arm to prevent the former Espanyol man from striking home the equalizer. Matias Silvestre then made a last-ditch intervention to deny the midfielder shortly after.
Guarin and Palacio then combined once more to great effect, with the Argentine getting on the end of the ex-Porto star's pass to make it 2-0. Guarin then reverted roles, this time finishing Antonio Cassano's through ball with aplomb to complete the rout.
And despite Nemanja Tomic's best efforts in injury time, grabbing the match's fourth goal, it did not deter the Nerazzurri from attaining a club-record 10th straight away victory.
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