Live updates: Follow the latest news on Israel-Gaza
Air Force One landed at Ben Gurion Airport on Wednesday morning, where Mr Biden was pictured embracing officials hours after more than 500 people were killed in an Israeli strike at Gaza's Al Ahli Arab hospital.
Israel has denied responsibility for the strike.
Mr Biden met Israeli Prime Minister Benjamin Netanyahu shortly after his arrival.
“Your visit is the first of a US President to Israel during a time of war. It is deeply moving,” Mr Netanyahu said.
“It speaks to the depth of your personal commitment to Israel … and to the Jewish people.”
Speaking in Tel Aviv, Mr Biden said he was “deeply outraged” by the attack and said Israel did not appear to be behind the explosion.
“Based on what I've seen, it was done by the other team, not you,” he said.
He focused on the US-Israel relationship, saying the US also mourns the 1,400 killed in Israel since October 7.
“Americans are grieving with you. The bravery and commitment of Israelis is stunning,” he said.
Mr Biden will also meet families of hostages held in Gaza, according to the White House, but will not travel to Jordan to meet Palestinian President Mahmoud Abbas.
A summit with Mr Abbas and Jordan's King Abdullah II was cancelled on Tuesday night as regional fury erupted following the attack on the Gaza hospital, pushing an already crumbling healthcare system past breaking point.
Doctors are reportedly operating on people without anaesthetic on hospital floors.
The strike prompted demonstrations in cities including Ramallah, Baghdad, Istanbul and Amman.
Outrage over Israel's recent actions has been growing, even before the attack on Al Ahli Arab Hospital as the UN and western powers urged humanitarian aid to be let through the Rafah crossing and condemned the displacement of more than one million people to the southern Gaza Strip.
Mr Biden will ask “tough questions” of Israel about its intentions in the coming weeks, National Security Council spokesman John Kirby said ahead of his arrival.
Speaking at a meeting of Israel's war cabinet, Mr Biden said the US “will continue to have Israel's back”.
“You are not alone,” he said. “75 years ago your founders declared that the nation would be based on freedom, justice and peace. The US stands with you in defence of that freedom, in pursuit of that justice and in support of that peace.”
The army held a press conference shortly before Mr Biden's arrival, deflecting blame for the hospital attack on Palestinian militants and their backer Iran.
“Iran funds Hamas but it 100 per cent funds Islamic Jihad,” said Israeli military spokesman Rear Admiral Daniel Hagari.
“Iran is behind these deaths.”
The army claimed the blast was the result of a failed rocket launch from a graveyard within the hospital compound, and shared a transcript of militants supposedly discussing the failed launch.
Admiral Hagari said Israel would provide satellite imagery confirming its claims to the US and other nations.
“The intelligence is credible. Our footage, imagery, those things will show credible to any liberal democracy,” he told reporters, saying there was “no direct Israeli hit” from land, sea or air.
The Episcopal Diocese of Jerusalem, which owns and runs the hospital, said it could not determine who was behind the attack, but said the hospital had received three evacuation warnings since Saturday.
It said approximately 5,000 people had sought shelter at the hospital on Saturday when more than a million people were told to leave the northern Gaza Strip.
Mr Netanyahu said Israel “will continue to ask people to move to safer areas”.
The US has reaffirmed its support for Israel in recent days, demonstrated by Secretary of State Antony Blinken's regional tour last week.
Although Mr Biden said Washington stands with Israel, he also said it must act within the confines of international law, adding an Israeli reoccupation of Gaza would be “a huge mistake”.