Barack Obama has said Israel has "no greater friend" than the US, as he makes his first visit to the country as president.
Arriving in Tel Aviv, Mr Obama told PM Benjamin Netanyahu the US was proud to be Israel's "strongest ally", and that "peace must come to the Holy Land".
On Thursday, Mr Obama will travel to the West Bank city of Ramallah to meet Palestinian President Mahmoud Abbas.
Peace talks, Syria and Iran's nuclear plans are expected to dominate talks.
But US officials have tried to lower expectations of any significant headway on restarting the Israeli-Palestinian peace process.
Correspondents say Israelis are more preoccupied with instability in the wider Middle East region than with breathing new life into the peace process, which broke down in 2010 amid a dispute over continued Israeli settlement construction.
Settlement supporters are a big force in Israel's new coalition government.
Mr Obama was welcomed by Mr Netanyahu and Israeli President Shimon Peres at Ben Gurion airport, where he was shown a missile battery that forms part of Israel's Iron Dome defence system against rocket attacks.
"Even as we are clear eyed about the difficulties, we will never lose sight of the vision of an Israel at peace with its neighbours," he said in brief comments.
He added: "The United States stands with Israel because it is in our fundamental security interests to stand with Israel. Our alliance is eternal. It is forever."
Mr Netanyahu thanked Mr Obama for "unequivocally affirming Israel's sovereign right to defend itself by itself against any threat".
Mr Obama later visited Mr Peres at his official residence where, in a joint news conference, the Israeli president said the two nations were united by a common vision - to confront dangers and bring peace.
Mr Peres said he trusted the US in its policy of preventing Iran from developing nuclear weapons.
President Obama said he had reassured Mr Peres "that in this work Israel will have no greater friend than the United States".
Mr Obama then went on to talks with Mr Netanyahu, with whom he has had a notoriously frosty relationship.
The main purpose of this trip is rebuild bridges and improving relationships which could give him more leverage over the new Israeli government, the BBC North America editor Mark Mardell reports.
The leaders' initial warm, if scripted, exchanges were a step towards doing that, our correspondent adds.
At home, Mr Obama has been criticised for not having visited Israel in his first term as president, with some saying it shows he is not close enough to the country. And one recent Israeli opinion poll suggested a mere 10% of the public had a favourable opinion of the US president.
On Thursday, Mr Obama will make a speech to Israeli university students, and travel to the West Bank to meet Palestinian President Mahmoud Abbas.
Security for the visit is tight, with thousands of Israeli and Palestinian security officers on duty in Jerusalem and the Palestinians' de facto capital in the West Bank city of Ramallah.
Both Israeli and Palestinian groups have staged protests in the run-up to Mr Obama's visit.
Some 200 activists pitched tents in the area known as E1, a stretch of land in East Jerusalem on which Israel controversially plans to build new houses. The Israeli move has been widely criticised, including by the US.
Abdullah Abu Rahma, a protest organiser, said they wanted to send a message to Mr Obama: "Enough with bias and support for Israel."
In the West Bank city of Hebron, protesters wearing masks of Mr Obama and civil rights leader Martin Luther King called for an end to "apartheid".
There were clashes between the pro-Palestinian protesters and some of the settlers living in the divided city, and a number of Palestinians were arrested.
In Gaza City, protesters burned US flags outside UN offices, the Associated Press reports.
Hamas spokesman Sami Abu Zuhri said the visit was "ominous" and unwelcome, and that its consequences would be negative.
"It gives legitimacy to the occupation and confirms the political support of the United States [to Israel]," AP quoted him as saying.
Meanwhile, Israelis have been staging protests in Jerusalem demanding Mr Obama free Jonathan Pollard, imprisoned in the US in 1987 for spying for Israel.