Security Unit 730 transported Netanyahu's family to safety as his Jerusalem home was stormed by protesters after he sacked Defense Minister Yaov Gallant for criticizing the government's controversial reforms of the judicial system.
Thousands rushed to the main Ayalon Highway in Tel Aviv and blocked it in both directions, the Times of Israel reported.
Israeli police used water cannons to push back protesters who broke through the barricades near Netanyahu's house.
Meanwhile, all universities across Israel announced a strike starting Monday over the controversial judicial reform plan.
Protest leaders have called for an emergency protest in Tel Aviv tonight after the sacking of Israel's defense minister.
News website Walla also reported protests in Haifa, northern Israel and in the southern city of Beersheba.
Israel has seen mass protests over the past 12 weeks against plans by the government for judicial reforms, which is seen by the opposition as a power grab in favor of the executive authority.