Biden has expressed "iron-clad" support for Israel in its war against Hamas over the bloody October 7 attacks and was welcomed on the tarmac by Prime Minister Benjamin Netanyahu.
But the horror of the hospital deaths threatened to derail his high-stakes visit, with Jordan cancelling a summit where King Abdullah II had been due to host Biden, Palestinian president Mahmud Abbas and Egyptian President Abdel Fattah al-Sisi.
The Palestinian Islamist militant movement Hamas said that an Israeli air strike destroyed the Gaza clinic, while Israel said a misfired rocket launched by the Islamic Jihad group had hit the Ahli Arab Hospital.
Between 200 and 300 people died, according to Gaza health authorities, while Hamas put the toll at more than 500 dead. Neither the Israeli nor the Palestinian accounts could be independently corroborated.
Shortly before Biden landed, Israeli military spokesman Daniel Hagari told a press conference that "evidence — which we are sharing with you all — confirms that the explosion at the hospital in Gaza was caused by an Islamic Jihad rocket that misfired."
"Our radar system tracked missiles fired by terrorists in Gaza at the time of the explosion and the trajectory analysis of the rockets shows the rockets were fired in close proximity to the hospital."
Middle East anger over the 12-day-old Gaza war, which has already killed thousands, has reached new heights after the hospital bloodshed, and protests against Israel were called in cities across much of the Arab and Muslim world.
Biden has strongly backed top ally Israel and its military campaign — retaliation for the killing of 1,400 people who were shot, mutilated or burnt to death in shock cross-border attacks launched by Hamas on October 7.
Israel's campaign to destroy Hamas and try to rescue 199 hostages from the besieged and blockaded territory had already left at least 3,000 dead inside Gaza before the hospital was destroyed.
Entire Gaza neighbourhoods have been razed and survivors are left with dwindling supplies of food, water and fuel, unable to flee the 40-kilometer (25-mile) long strip that has been blockaded since 2007 by Israel and Egypt.
"The situation in Gaza is spiralling out of control," UN World Health Organization chief Tedros Adhanom Ghebreyesus wrote on X, formerly Twitter. "We need violence on all sides to stop."
- Hospital carnage -
On the ground in Gaza, the blast at the Christian-run hospital brought new chaos and suffering Tuesday night, as the dead were pulled from the rubble and the wounded were rushed to nearby medical centres.
Scores of bodies cloaked in blood-stained sheets and white plastic wrap soon lined the floors at the nearby the Al-Shifa hospital, where stunned and bereaved relatives tried to identify loved ones.
The Palestine Red Crescent Society said hundreds died including women, children, staff and "internally displaced people seeking safe shelter."
Ghassan Abu Sittah, a doctor with the charity Doctors Without Borders (MSF), recounted that "we were operating in the hospital. There was a strong explosion and the ceiling fell on the operating room."
"Hospitals are not a target," he said. "This bloodshed must stop. Enough is enough."
The Archbishop of Canterbury Justin Welby represents the Anglican church, which runs the Ahli Arab Hospital.
He said the hospital was one of several medical facilities in northern Gaza subject to evacuation orders and that it had already been hit by "Israeli rocket fire" on October 14, which wounded four staff.
According to World Health Organisation figures, there have been more than 100 attacks on hospitals, ambulances and other health care assets since October 7.
News of the hospital's destruction brought swift international condemnation.
EU foreign policy chief Josep Borrell said "responsibility for this crime must be clearly established" and the "perpetrators held accountable."
United Nations Secretary-General Antonio Guterres called for an "immediate humanitarian ceasefire" and warned Israel against "the collective punishment of the Palestinian people."
- 'Day of Rage' -
Across the region, the response was quick and furious as protesters tried to storm the Israeli embassy in Jordan, a country home to millions of Palestinian refugees.
In Lebanon, demonstrators clashed with security forces outside the US embassy. Stones were hurled and a building was set on fire.
The US State Department authorized the departure of "some non-emergency" personnel from the Beirut embassy, citing the "unpredictable security situation."
In Lebanon, Hezbollah vowed a "day of rage" on Wednesday, one of many countries across the region where street protests were expected.
Jordanian Foreign Minister Ayman Safadi said the cancelled four-way summit in Amman would be held "when the decision to stop the war and put an end to these massacres has been taken."
The White House confirmed late Tuesday that Biden's visit would go ahead to Israel, where he was expected to express solidarity over the Hamas attacks, in which 31 Americans were among the dead.
The attacks were the deadliest in Israel's 75-year history, carrying painful echoes of past pogroms and undermining faith in the country's security services.
The United States and Israel have been at pains to try to deter Israel's declared enemies — chiefly Iran and its Lebanon-based ally Hezbollah -- from escalating the conflict.
Biden was also expected to press for steps to minimize the huge humanitarian impact of Israel's military response on civilians and allow aid to enter the besieged Gaza Strip.
Speaking aboard Air Force One, White House National Security Council spokesman John Kirby said Biden would ask Netanyahu "tough questions" about the path ahead.
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