Organisers said as many as 100,000 people attended the Sunday night rally, but police estimates put the number at 50,000 to 60,000.
The huge rally was organised by the powerful council of Jewish settlements in the West Bank and Gaza Strip - known by its Hebrew acronym YISHA - and held under the slogan: "The disengagement plan is tearing the nation apart."
Demonstrators held signs reading "Sharon is dictator" and "You must resign now". One sign called Sharon a "traitor", but organisers hastened to take that one down.
Call to split
Speakers urged the National Religious Party, known as Mifdal, to withdraw from the government immediately.
The party was due to make a decision on whether to remain in the government.
During the rally, settler leaders castigated Sharon's plan, calling it "ethnic cleansing of Jews" and "a crime against humanity".
Protesters called Sharon a
dictator and pressed him to quit
The very same leaders, including prominent rabbis, routinely call on the Israeli government to expel Palestinians from the West Bank and Gaza and, if necessary, physically annihilate them.
Last week, a group of YISHA's rabbis issued a religious edict urging the Israeli army not to spare Palestinian civilians in what they called the "war on terror".
After the rally, thousands of protesters holding candles walked to Sharon's residence, demanding that he should "listen to the voice of the people".
But according to opinion polls, as many as 70% of Israeli citizens support the disengagement plan to pull out from Gaza.
Gush Emunim (Bloc of the Faithful), with which most settlers are affiliated, fiercely opposes any peaceful arrangement with the Palestinians involving territorial concessions.
The movement espouses the idea that all mandatory Palestine (extending from the River Jordan to the Mediterranean) belongs exclusively to the Jews by a divine decision and that no Israeli government has the right or authority to "give up" any part of the land of Israel to "goyem" (derogatory for non-Jews).
Civil war fears
Hours before the rally, Sharon lashed out at his right-wing opponents, accusing them of trying to incite civil war.
He called on his cabinet ministers to do what was necessary to foil the settlers' threats.
The prime minister was referring to warnings voiced by some right-wing activists this week that settlers would confront Israeli soldiers and security personnel trying to evict them from their homes in the Gaza settlements.
Opinion polls say 70% of Israelis
support Sharon's pullout plan
Some Israeli commentators have predicted that the settlers might embark on a "spectacular singular act" to thwart Sharon's disengagement plan should it go ahead despite their fierce opposition.
This act, they argue, could take the form of an attack on the al-Aqsa mosque in East Jerusalem, considered one of Islam's holiest places, or an attempt to assassinate Sharon.
Some of the right-wing leaders have called on Sharon to organise a referendum on his plan to withdraw from Gaza or go for early elections.
While opinion polls suggest Sharon's disengagement plan has the support of nearly three-quarters of the Israeli public, the prime minister dreads the prospect of his Likud party disintegrating should he decide to hold a referendum.
The Likud, which has many pro-settler activist members, is overwhelmingly opposed to Sharon's plan.