Lautaro Martinez made his first league start following his return from suspension whilst Alexis Sanchez dropped to the bench.
Inter looked lively from the onset as Diego Godin toweringly headed over the top of Thomas Strakosha's goal although Daniele Padelli was given a big scare as Sergej Milinkovic-Savic rattled the frame of the woodwork with a thunderous strike from the edge of the six-yard area all inside the opening 10 minutes.
A flowing move through the middle from Marcelo Brozovic ended with Romelu Lukaku, who forced Strakosha to a low save with a powerful strike from the near side 18 minutes in.
Inter drew first blood two minutes before halftime after Ashley Young volleyed home a rebound from inside the area after Straskosha struggled to handle Antonio Candreva's shot.
The home side were given a lifeline after the break by the Video Assistant Referee as De Vrij tripped Ciro Immboile in the area for a penalty, which the latter tucked away.
Inter regained positivity a little later and were on the attack through Lukaku's near post strike and a glancing header from Matias Vecino.
Lazio took the lead in the last 20 minutes after Milinkovic-Savic controlled inside the area to slot into the bottom corner.
The Nerazzurri went for an all-out attacking dimension in the remaining minutes and with that introduced Christian Eriksen and Victor Moses.
This changes did not pay off and Inter nearly conceded a third goal late on after Immobile sliced through the defence to bring Padelli to a point-blank save, but 2-1 was how the encounter ended as Lazio move into second spot, with Antonio Conte's men dropping to third.