Antonio Conte called the Spurs players "selfish" and criticised the club's culture in a remarkable news conference after their recent draw at Southampton.
Tottenham are fourth in the top flight but are out of all cup competitions.
Conte's assistant Cristian Stellini will step up as head coach for the rest of the season, with former midfielder Ryan Mason his assistant.
His departure means Spurs are searching for their fourth permanent manager in four years since Mauricio Pochettino left in 2019
The former Spurs boss, Antonio Conte said his team "don't want to help each other" after a 3-3 draw at Southampton on Saturday.
"Tottenham's story is this - 20 years there is this owner and they never won something. Why?" Conte said.
Spurs had led by two goals at St Mary's but conceded twice in 15 minutes.
"The fault is only for the club, or for every manager that stay here?" said Antonio Conte. "I have seen the managers that Tottenham had on the bench. You risk to disrupt the figure of the manager and to protect the other situation in every moment.
"Until now I try to hide the situation but not now because, I repeat, I don't want to see what I have seen today because this is unacceptable and also unacceptable for the fans."
Tottenham have won one trophy since the ownership group, chaired by Daniel Levy, took over the club in 2001 - the League Cup in 2008.
They have had 11 different managers in that time, including three since the 2019 departure of Mauricio Pochettino, who took them to the Champions League final before being sacked six months later.
Spurs are out of all cup competitions this season with Sheffield United knocking them out of the FA Cup before AC Milan ended their Champions League hopes - and AntonioConte said it is time for the club and players to start taking responsibility.