Napoli conquered the blue half of the Olimpico for the first time in five years. Gonzalo Higuain, Goran Pandev and Jose Callejon did the damage for Rafa Benitez's side, who snapped a run of three consecutive defeats in all competitions to go six points behind league leaders Juventus.
Higuain netted twice, while Pandev returned to haunt his former club on his 300th Serie A appearance. Valon Behrami had earlier turned into his own net to level the scores at the break. Keita Balde reduced the arrears to give Lazio hope late on, before Callejon sealed the result at the death.
Lazio slump to five league games without a win, and despite ensuring progress in the Europa League in midweek, Vladimir Petkovic will face fresh speculation about his immediate future in charge of the Eagles.
Miroslav Klose was still out with a shoulder injury, so youngster Brayan Perea led the Lazio forward line. Injured trio Juan Carlos Zuniga, Giandomenico Mesto and Marek Hamsik missed out for Napoli.
Higuain threatened Lazio's high backline early on, but two through balls were called back for marginal offside decisions.
Antonio Candreva went close for Lazio on six minutes. Senad Lulic's cross-field pass was collected by the winger, who cut inside onto his left foot and missed the far post by a fraction.
Federico Marchetti tipped over a speculative cross-turned shot from Callejon, while Hernanes didn't get enough power to test Pepe Reina from 18 yards. The goalkeeper cut out Candreva's dangerous cross from the byline, then did well to catch a dipping shot from the lively winger, who was getting the better of marker Pablo Armero on every foray forward.
The Eagles were enjoying a good spell. Perea teed up Abdoulay Konko to shoot wide, but Napoli produced a sting in the tail. A moment of individual brilliance by Higuain put the visitors ahead on 24 minutes. The Argentine showed a great turn of pace as he picked the ball up from the halfway line, holding off Michael Ciani and poking the ball underneath Marchetti.
Lazio were level less than a minute later. Candreva evaded Armero yet again. His cross from the right was met by Perea, whose flick ricocheted in off Behrami against his former club to boot.
Napoli had a goal chalked off eight minutes before the break. Marchetti parried Lorenzo Insigne's drive and Higuain tapped in, but was ruled offside. Replays showed the referee made the right decision.
Moments later, the ball fell invitingly for Hernanes in the box. Reina rushed out to close the angle, but the Brazilian lost his footing and sliced wide.
Armero's nightmare continued when Candreva dispossessed him right on the stroke of half time. With no-one to cross to, Candreva burst down the right wing and flashed wide from a difficult angle.
Hernanes saw a shot fade past the post moments after the restart, but Napoli re-took the lead after the Lazio defence were left wanting. Higuain pulled away to collect a free kick floated out wide. His cross was nodded down by Christian Maggio, allowing Pandev to swivel and fire into the net from close range.
The goal gave Napoli confidence and swung the momentum in their favour. Pandev found Higuain in space on the hour and he put the ball through Marchetti's legs but wide of the far post.
Lazio made attacking changes, only to leave spaces at the back and Napoli took full advantage. Higuain got a second goal 18 minutes from the end. Pandev picked out his strike partner, whose deft touch took him past Lorik Cana and left him one-on-one. The frontman made no mistake as he blasted the ball past Marchetti.
A cautious Benitez took off his forwards and Lazio found a way back into the game. Substitute Keita Balde dribbled across the 18 yard box and hammered home to hand the home side a lifeline with two minutes left to play.
The optimism was short-lived as Napoli restored their two goal cushion in stoppage time. Dries Mertens dispossessed Ciani and played the ball to Callejon, who slid the ball inside the far post. The boo-boys made themselves heard at the final whistle as Petkovic and Lazio were whistled off the pitch.
Lazio: Marchetti; Konko, Ciani, Cana, Radu; Biglia; (Onazi 82) Candreva, Gonzalez, (Floccari 62) Hernanes, Lulic; (Keita 70) Perea
Napoli: Reina; Maggio, Albiol, Britos, Armero; Inler, Behrami; Insigne, Pandev, (Dzemaili 74) Callejon; (Bariti 90+3) Higuain (Mertens 85)
Goals: Higuain 24, 72 (N) Behrami og 25 (L) Pandev 50 (N) Keita 88 (L) Callejon 90 +1 (N)