Ciro Immobile headed the hosts in front in the first half before Luis Alberto swept home a second after the break to lift the Biancocelesti into eighth place, two points behind Napoli in fifth.
The result was a welcome relief to Simone Inzaghi after picking up just one win in their last four games, including a defeat and a draw in their last two against Verona and Benevento respectively.
Both sides were missing key players, as Francesco Acerbi and Joaquin Correa were ruled out with injury close to kick-off for the Aquile and the visitors were missing injured pair Dries Mertens and Victor Osimhen as well as suspended captain Lorenzo Insigne.
Immobile threatened early on when he volleyed narrowly over the bar, and the Italy international soon made the breakthrough with a superb looping header into the top corner from an Adam Marusic cross.
Napoli hit back as Fabian Ruiz and Piotr Zielinski were both denied by flying saves from former Partenopei goalkeeper Pepe Reina within the space of two minutes.
But Lazio doubled their lead 10 minutes into the second half when Alberto raced onto an Immobile pass to curl an unstoppable finish into the corner of the net.
Gennaro Gattuso’s hopes of seeing his side fight their way back were dealt a blow when Hirving Lozano was carried off the pitch with ice strapped to his injured ankle, but Andrea Petagna mustered an effort when his low drive forced Reina into a save.