Walter Mazzarri's side failed to produce the sparkling form which has been a highlight of the early stages of the Serie A season, thanks to a dogged performance from Ciro Ferrera's side.
Mazzarri grew increasingly angry during the opening half, and was sent to the stands in a rage after reacting to a challenge on Swiss midfielder Valon Behrami.
A sweeping move from the away team found Marek Hamsik in space in the area, and he forced a rash challenge from Daniele Gastaldello to win a penalty.
Gastaldello was given a straight red for the late tackle, with Edinson Cavani making no mistake from the spot for his fifth goal of the season.
Sampdoria were forced to chase the game late on but the ten men could not find a response.
A spirited win for Napoli has moved them level on points with Juventus at the top of the Serie A table.