The Belgian struck twice in quick succession to hand Sinisa Mihajlovic his first loss in charge of Sampdoria. The Serb had enjoyed a six game unbeaten run in all competitions before today and saw his side hit the woodwork twice en route to defeat.
Napoli were without injured quintet Pepe Reina, Giandomenico Mesto, Juan Zuniga, Marek Hamsik and Valon Behrami. Sampdoria welcomed back Manolo Gabbiadini from suspension. Both sides set their stalls out to attack during an entertaining and open match.
Angelo Da Costa smothered Jose Callejon's weak backheel, then got down to his near post to deny Mertens. Da Costa instinctively denied Gonzalo Higuain from six yards, after the Argentine's volley ricocheted off the goalkeeper's knee.
Nenad Krsticic did find the back of the net on 13 minutes, but the effort was correctly ruled out for offside. Eder had demonstrated some neat one touch play in the build up.
Callejon dribbled through traffic and curled over from 18 yards. Krsticic threatened once more after running onto Angelo Palombo's through ball. However, he took a poor first touch as he rounded Rafael and the chance came to nothing.
Mertens was at the heart of Napoli's counter attacks. He tested Da Costa from 25 yards, before failing to reach Higuain's wayward shot which flashed across the box.
Eder turned in the box and volleyed over Lorenzo De Silvestri's cross just past the half hour. The Brazilian was thwarted again when Rafael saved a deflected effort. Napoli quickly broke through Higuain, but his pinpoint cross was swept over by Callejon.
Three minutes after the break, Eder turned Federico Fernandez inside out in the box, only to shoot straight at Rafael. Napoli were forced into a change when Anthony Reveillere went off injured, but they hit the front on 53 minutes. Callejon slipped in Higuain, whose drilled pass was placed into the bottom corner by Mertens. The midfielder demonstrated good control, keeping his first time shot low to give Da Costa no chance.
Samp reacted positive to going a goal down. Gabbiadini cut inside Pablo Armero and rattled the crossbar. Rafael was well beaten as the ball hit the underside of the goal frame and bounced clear. Moments later, Armero was lucky not to give a penalty away after he looked to pull Vasco Regini down in the box.
Napoli doubled their advantage just past the hour. Da Costa pushed Mertens' 25-yard free kick into the net after getting a hand to the effort. The goalkeeper really should have done better.
Nicola Pozzi came on for his 100th Sampdoria appearance and he almost made an instant impression. His curled shot beat Rafael, but not the woodwork. The ball bounced off both posts before rolling into Rafael's grateful hands.
Da Costa denied Callejon from close range and Insigne bent a shot wide of the far post, as Napoli chased a third goal. In stoppage time, brave goalkeeping from Rafael denied Eder after a melee in the box.
Napoli: Rafael; Maggio, Fernandez, Albiol, Reveillere; (Armero 49) Inler, Dzemaili; Mertens, Callejon, (Radosevic 84) Insigne; Higuain (Zapata 77)
Sampdoria: Da Costa; De Silvestri, Mustafi, Gastaldello, Regini; (Costa 72) Obiang, Palombo; Gabbiadini, Krsticic, (Pozzi 77) Soriano; (G.Sansone 66) Eder
Goals: Mertens 53, 62 (N)