"Napoli announce that they have relieved Edoardo Reja of his duties as first team coach and have appointed Roberto Donadoni," a club statement said.
"The club has taken this decision with a heavy heart given the fundamental role of Reja during the last five seasons, where Napoli were propelled from Serie C to Serie A and the UEFA Cup."
Mid-table Napoli, who were bidding for a Champions League place after a bright start to the season, lost 2-0 at home to Lazio on Sunday to extend their winless league run to nine.
They were eliminated from the UEFA Cup 4-3 on aggregate by Benfica in the first round last October.
Former Italy and AC Milan midfielder Donadoni, who previously coached Livorno, was sacked as Italy coach in June after his lacklustre side were knocked out of Euro 2008 by winners Spain on penalties in the quarter-finals.
Napoli, backed by a huge fan base and the money of film producer Aurelio De Laurentiis, are in their second season back in the top flight and have two of Serie A's hottest prospects -- Slovakia's Marek Hamsik and Argentina forward Ezequiel Lavezzi.
The club from Naples, Italy's third biggest city, won their only two scudettos in 1987 and 1990 thanks to the skills of Diego Maradona.
