They tore down a security wall around the 21-storey building and dumped hundreds of documents out of the windows.
More than 500 people were injured as protesters clashed with security forces backed by armored cars overnight, health officials said.
The unrest began after Friday prayers when thousands of people gathered in Cairo’s central Tahrir Square, calling on the ruling military council to speed up the pace of political reform following the ouster of former President Hosni Mubarak in February.
Hundreds later marched on the embassy and used sledgehammers and iron bars to destroy the graffiti-covered wall.
Egyptian state media said several police vehicles were set alight.
Police used tear gas and there were reports of gunshots being heard nearby.
Israeli ambassador Yitzhak Levanon, his family and other embassy staff have returned to Israel aboard a military plane, Sky News reported.
The Guardian quoted an Israeli official as saying that a group of 30 protesters reached a room at the top of the building just before midnight and threw Hebrew-language documents of the windows.
Egyptian Prime Minister Essam Sharif summoned a crisis cabinet meeting.
An interior ministry official said "foreign hands" were behind the violence, in comments carried by state television.
U.S. President Barack Obama called on Egypt to honor its international and safeguard the mission after Israel requested help from Washington to try to defend the building.
"The President expressed his great concern about the situation at the embassy, and the security of the Israelis serving there," a White House statement said.
There have been daily protests outside the Israeli embassy since five Egyptian border guards were killed by Israeli forces on August 18, as they pursued suspected militants across the border.
The gunmen had earlier that day attacked Israeli civilian buses in southern Israel, killing eight people.
Israel said it regretted the deaths of the Egyptian policemen but denied responsibility.
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