The surviving ex-Mossad intelligence agency chiefs voiced their opinion of the fourth-term, right-wing leader in a joint interview excerpted on the front page of Yedioth Ahronoth, Israel's best-selling newspaper and a regular Netanyahu critic.
Netanyahu had no immediate response, but a senior member of his governing coalition brushed off the censure.
Danny Yatom, who headed the Mossad during Netanyahu's first stint in office in the late 1990s, called for his ouster, accusing him and his aides of "putting their interests ahead of national interests" as corruption investigations deepen.
Police questioned Netanyahu on Monday over his alleged dealings with the country's largest telecommunication company, one of three cases weighing on his political future. Netanyahu has denied any wrongdoing and opinion polls show his popularity is still high.
Yatom also voiced concern about "the inertia in the diplomatic sphere, which is leading us toward a bi-national state (with the Palestinians), which would spell the end of (Israel as) a Jewish and democratic state".
Negotiations over a "two-state solution" to Israel's conflict with the Palestinians have been frozen since 2014. Some argue that if Israel fails to quit occupied territory, it could one day face a choice between remaining a democracy or securing a Jewish majority by denying the Palestinians voting rights.
Figures cited by Israeli officials on Monday showed the number of Jews and Arabs between the Mediterranean Sea and the Jordan River - territory encompassing Israel, the occupied West Bank and the Gaza Strip - is at or near parity.
"We are in a critical medical state. It could be that the country had symptoms when Netanyahu took over, but he has brought it to the grave condition of a malignant disease."
Netanyahu's office did not immediately respond.
Education Minister Naftali Bennett, a hardliner in Israel's conservative coalition government, took to Twitter to dismiss the allegations aired by the ex-spymasters as "simply untrue".
"The country is in an excellent condition," said Bennett, who has cast himself as a possible successor to Netanyahu.
"Among most of our leadership, the good of the country is first and foremost .... Israel is going in a good direction!"
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