"FC Internazionale Milano have decided to relieve coach Hector Cuper of his duties," the club said on their official website.
Cuper, in his third season at Inter, had been warned by chairman Massimo Moratti that further setbacks would not be tolerated after the 3-1 derby defeat by rivals AC Milan two weeks ago.
Assistant coach Corrado Verdelli, who has enjoyed success with Inter's youth team, takes charge temporarily for the Champions League game against Lokomotive Moscow on Tuesday
Former AC Milan and Lazio coach Alberto Zaccheroni is the favourite to the land the job on a permanent basis.
Although Inter came back from two goals down for a 2-2 draw at Brescia on Saturday, the result, Inter's fourth game om a row without a win in Serie A, was not enough to keep Cuper his job.
Cuper, a former Argentina central defender, took over at Inter in June 2001 after coaching stints in Argentina and at Real Mallorca and Valencia in Spain.
LONG WAIT
Having taken Valencia to two runners-up spots in the Champions League in successive seasons, he was charged with the task of ending Inter's long wait for an Italian title.
Inter last won in 1989 and Moratti had tried several coaches including Marcello Lippi, Roy Hodgson and Marco Tardelli in his bid to bring back the glory day's of the 1960's when his father Angelo
The goal was almost reached in Cuper's first season at Inter but the title was thrown away on the final day of the season with a 4-2 defeat at Lazio handing the title to Juventus.
Last year Inter finished second in Serie A and reached the semi-finals of the Champions League where they were knocked out on the away goals rule by city rivals Milan.
Despite criticism of Cuper in the press, Inter's fans stood by the coach and Moratti insisted that he had faith in Cuper bringing in wingers Andy van der Meyde and Kily Gonzalez during the close season to add the quality wide players that the coach had requested.
This season began well with two wins in Serie A and then a stunning 3-0 victory away to Arsenal in the Champions League.
But goalless draws with Sampdoria and Udinese were followed by the derby defeat by Milan which continued Cuper's poor run of results in games against direct title rivals.
Although the comeback at Brescia showed spirit, the result leaves Inter in sixth place already seven points behind leaders Juventus after just six games.
Cuper's Argentine support staff have also been dismissed.
"The club would like to thank the Argentine coach, his assistant Oscar Armando Cavallero and athletic trainer Juan Manuel Alfano for their work.
"Corrado Verdelli will take charge of the first team for Tuesday's Champions League match away to Lokomotiv Moscow," the club said.