Jose Callejon scored a trademark close-range goal midway through the first half, with Lorenzo Insigne thoroughly atoning for a poor miss by bagging a second-half brace for Napoli.
While there are still seven games to play and with them 21 points to fight for, the Azzurri look best placed to finish third given their scoring prowess and superior head-to-head record with Lazio.
However, Simone Inzaghi's men will play three of Serie A's bottom five over the run-in, while Napoli's remaining opponents are mostly mid-table outfits including Torino and Sampdoria.
With their vociferous supporters roaring them on at the Stadio Olimpico, Lazio made a lively start.
Six minutes in Felipe Anderson made up ground to cross for Stefan Milinkovic-Savic, whose shot on the volley almost forced Kalidou Koulibaly to score an own goal with his wild, sliced clearance.
Napoli steadily began to take control, though, and come the 25th minute they had an opener.
Dries Mertens slipped the ball through to Marek Hamsik, with the Slovakian schemer delivering a daisy-cutting assist to the far post that Callejon pinged home with a deft touch.
Lazio bit back when Felipe Anderson wriggled into the box to test Jose Reina, but they could not equalise before the break.
Read the full article on eurosport.co.uk: Napoli take stranglehold on Champions League place