Kerry flew in from Cairo despite US and European bans on flights into Ben Gurion airport, with reporters embargoed from reporting the trip until his customised Boeing 757 touched down.
He immediately set off for Jerusalem, where he was to meet for talks with UN chief Ban Ki-moon, who is also in the region on a push for peace.
Kerry will then travel to the West Bank city of Ramallah for talks with Palestinian leader Mahmoud Abbas, a State Department official said.
He will later return to Tel Aviv for talks at the defence ministry with Israeli Prime Minister Benjamin Netanyahu, the official said, adding that Kerry had been engaged in phone calls with regional foreign ministers until the early hours of Wednesday.
Washington's top diplomat has urged all sides to embrace an Egyptian ceasefire initiative that would halt the fighting before the start of negotiations, AFP reported.