Napoli needed a soft penalty to break down Empoli before Piotr Zielinski rounded out the scoreline for their 10th straight Serie A victory.
The Partenopei had lost their last three league meetings with Empoli. Kvicha Kvaratskhelia and Amir Rrahmani were still out injured, while the Tuscans missed Mattia Destro, Koni De Winter and Lorenzo Tonelli.
Guglielmo Vicario smothered the Giovanni Di Lorenzo pull-back from the by-line, but the first real shot on target was on 38 minutes with Giacomo Raspadori, his control and strike on a Di Lorenzo cross.
On the stroke of half-time, Raspadori came within inches of opening the scoring with an effort that grazed the upright.
Osimhen’s header and an Andre-Frank Zambo Anguissa shot from a Raspadori assist were over the bar, as was the Bandinelli scorcher from the edge of the area for Empoli.
Tanguy Ndombele fired straight at Vicario, while Osimhen towered above the crowd only for his header to go over from a Politano free kick.
The breakthrough came when Osimhen caught Razvan Marin napping and placed himself in front to shield the ball, forcing the midfielder to bump into the back of him for a penalty. Chucky Lozano had just come on and insisted on taking the spot-kick, which went in despite Vicario getting a hand to it.
Things got even worse for Empoli five minutes later when Sebastiano Luperto, a former Napoli defender, received his second yellow card for a late tackle on Lozano.
Alberto Grassi made an acrobatic goal-line clearance to keep out Osimhen’s header on a looping Mario Rui cross.
Piotr Zielinski fired one chance over, but didn’t miss the second from 12 yards on the volley from Lozano’s cross.
Empoli still forced an Alex Meret save in stoppages with Nedim Bajrami at the near post.
Napoli 2-0 Empoli
Lozano pen 69 (N), Zielinski 88 (N)
Sent off: Luperto 74 (E)