Mike Pence has kicked off his visit to Israel by saying it was an honour "to be in Israel's capital, Jerusalem".
The US vice president has met with Israel's Prime Minister Benjamin Netanyahu but has been snubbed by the Palestinian President, angry about Donald Trump's controversial recognition of Jerusalem as the Israeli capital.
Mr Pence received a warm welcome and placed his right hand over his heart as an honour guard greeted him with the American national anthem.
Mr Netanyahu lauded the American-Israeli alliance, which he said has "never been stronger".
Israel has praised the decision taken by Mr Trump on 6 December, but the move angered Palestinians, causing Palestinian President Mahmoud Abbas to refuse a meeting with Mr Pence.
Mr Abbas says America can no longer serve as mediator in Middle East peace talks. The Palestinians are planning a general strike on Tuesday to protest Mr Trump's declaration.
Violent protests since Mr Trump's announcement has left at least 17 Palestinians dead, mostly in clashes with Israeli forces. One Israeli has been killed in that time.
Mr Netanyahu said on Sunday night, referring to Mr Abbas by his Arabic nickname: "Regarding peace, I have a message to Abu Mazen.
"There's no substitute to the American leadership in leading the diplomatic process.
"Whoever won't discuss peace with the Americans doesn't want peace."
Mr Abbas is due to meet EU foreign ministers in Brussels on Monday while Mr Pence is in Israel, and is expected to ask them to officially recognise the state of Palestine "as a way to respond" to Mr Trump's announcement.
Mr Pence will address the Israeli parliament later on Monday, but his speech will be boycotted by Israeli Arab politicians, who call him "dangerous and messianic".
His visit is the final leg of a trip that has included talks in Egypt and Jordan.
Mr Trump's decision has also caused concern among other Arab states.
In Amman on Sunday, Jordan's King Abdullah II, one of America's key allies, said: "Jerusalem is key to Muslims and Christians as it is to Jews… It is key to peace in the region. And key to enabling Muslims to effectively fight some of the root causes of radicalisation."
Mr Pence, a devout Christian, will visit Jerusalem's Western Wall on Tuesday, one of the holiest sites in Judaism.
Jerusalem is home to sites which are holy to Muslims, Jews and Christians.
Israel insists it has been the capital of the Jewish people for 3,000 years and the country's capital for 70 years.
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However, Palestinians want East Jerusalem to be the capital of their future state, which Israel captured and annexed in 1967.
Mr Trump's decision has been interpreted by his critics as America taking Israel's side in the conflict.