It is Cameron's first official visit since the Conservative leader took over as premier in 2010.
After landing at Ben Gurion airport near Tel Aviv, Cameron went straight to Jerusalem to meet Prime Minister Benjamin Netanyahu for talks focusing on "Iran's military nuclear programme, the peace process and bilateral ties," an aide to the Israeli leader said.
On Thursday, he was to meet with Palestinian leader Mahmud Abbas in the southern West Bank city of Bethlehem, Palestinian officials said.
Ahead of his arrival, Downing Street said Cameron would focus on the opportunities that a peace agreement would bring.
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"Secretary Kerry's efforts to secure agreement on a negotiating framework that could lead to peace are entering a critical phase. And I'll be using my visit to support those peace efforts," Cameron was quoted as saying before leaving London.
He said he would encourage both leaders "to take the final difficult steps towards peace" which could offer both sides a future that was both secure and prosperous.
He was also to impress on Cameron on the need for Europe to push the Palestinians "to change their current behaviour" in the peace talks, the Jerusalem Post newspaper said. Israel has blamed Palestinian "intransigence" for blocking progress in the negotiations.