The Spaniard, who has had a seven-month stint at Chelsea, was announced as the new coach of the Partenopei on Monday.
"Rafa Benitez is the new coach of Napoli. An agreement was signed [on Monday] in London," the club wrote in an official statement on its website. "Napoli are happy to welcome a coach so prestigious to our own family."
Benitez won the Europa League this season with Chelsea and stepped in for Roberto Di Matteo to guide the Blues to a Champions League place. He is set to take over for Mazzarri, who left the Partenopei to join Inter Milan after coach Andrea Stramaccioni was sacked for a disappointing ninth-place finish this term.
Benitez' last two games in charge of Chelsea came in the United States, during a pair of high-scoring friendly losses to Manchester City in St. Louis and New York City.
Napoli president Aurelio De Laurentiis revealed via Twitter that he was delighted to get the 53-year-old.
"Rafa Benitez is the new coach of Napoli. A man of great international experience. A leader," De Laurentiis wrote.
The Spaniard has coached in Italy before, but had a rather unsuccessful spell at Inter lasting just six months in the job after being successor to Jose Mourinho's treble-winning side.