There are fears of more loss of life after 58 Palestinians were shot dead and 2,400 injured when Israeli troops opened fire on protesters near the Gaza border.
Monday's protests intensified as the new US embassy was inaugurated in Jerusalem, marking the deadliest day in the region since the 2014 cross-border war.
Palestinian health officials, who announced the death and injury tolls, said five of those killed were children.
Of the injured, officials said at least 1,200 Palestinians were shot and wounded - 116 of who were in serious or critical conditions - while others suffered other types of injuries, including from tear gas.
- Video report by ITV News Correspondent Emma Murphy
The Israeli military said 40,000 protesters are taking part in demonstrations at 12 points along the Gaza border in a show of anger at the inauguration of the new US embassy in Jerusalem.
The deaths came as Donald Trump declared Monday a "great day" for Israel as his top aides celebrated the opening of the embassy as a campaign promised fulfilled.
As the embassy was opened, Israel's Prime Minister said Jerusalem would always be the "eternal, undivided" capital of Israel, and proclaimed it a "glorious day".
Benjamin Netanyahu also thanked President Trump for showing the "courage" to keep a key campaign promise and said relations with the US had never been stronger.
- Video report by ITV News Senior International Correspondent John Irvine
However, the UN human rights chief said that the "shocking killing of dozens" due to "Israeli live fire in Gaza must stop now" and demanded respect for human life.
Zeid Ra'ad al-Hussein continued that perpetrators of "outrageous human rights violations" must be held to account.
Monday's march is thought to be the biggest yet in a long campaign against a decade-old blockade of the territory.
The relocation of the embassy from Tel Aviv has infuriated the Palestinians, who seek east Jerusalem as a future capital.
Monday marked the biggest showdown in recent weeks between Israel’s military and Gaza’s Hamas rulers along the volatile border.
It is the culmination of a campaign, led by the Islamic militants Hamas and fuelled by despair among Gaza’s two million people, to break the blockade of the border territory by Israel and Egypt.
Since weekly border marches began in late March, 83 Palestinian protesters have been killed and more than 2,500 wounded by Israeli army fire.
Hamas leaders have suggested a border breach is possible on Monday, while Israel has warned it would prevent protesters from breaking through the barrier at any cost.
Following Monday's deaths, the EU has called on Israel to respect the "principle of proportionality in the use of force".
Foreign Policy Chief Federica Mogherini said that both sides should act "with utmost restraint to avoid further loss of life" and added that "Israel must respect the right to peaceful protest".
At the same time, she insisted that Hamas must make sure demonstrators in Gaza are peaceful and "must not exploit them for other means."
Israeli military spokesman Lt Col Jonathan Conricus said the army had bolstered its front-line forces along the border, but also set up additional “layers” of security in and around neighbouring communities to defend Israeli civilians in case of a mass breach.
He said there had already been several “significant attempts” to break through the fence.
“Even if the fence is breached, we will be able to protect Israeli civilians from attempts to massacre or kidnap or kill them,” he said.
The US said it chose the inauguration date to coincide with the 70th anniversary of Israel’s establishment.
But it also marks the anniversary of what Palestinians call their “nakba”, or catastrophe, a reference to the uprooting of hundreds of thousands who fled or were expelled from what is now Israel during the 1948 war surrounding Israel’s independence.
A majority of Gaza’s two million people are descendants of refugees, and the protests have been billed as the “Great March of Return”.
Leaflets dropped over Gaza by army jets warned that those approaching the border “jeopardise” their lives. The warning said the army is “prepared to face all scenarios and will act against every attempt to damage the security fence or harm IDF soldiers or Israeli civilians”.
In Jerusalem, top officials in US president Donald Trump’s administration attended events linked to the inauguration of the embassy.
US treasury secretary Steven Mnuchin said that it was a US “national security priority” to move the embassy from Tel Aviv to Jerusalem.
Mr Trump’s decision to go forward with a campaign promise to move the American embassy from Tel Aviv to Jerusalem was welcomed by Israel and condemned by the Palestinians.
Previous US presidents had signed a waiver postponing the move, citing national security.
Israel captured east Jerusalem in the 1967 Middle East war and annexed it in a move not recognised by the international community.
The Palestinians seek the city’s eastern half as the capital of a future state.
Palestinian president Mahmoud Abbas cut ties with the Trump administration and declared it unfit to remain in its role as the sole mediator in peace talks.
Israeli prime minister Benjamin Netanyahu praised Mr Trump’s “bold decision” in upending decades of US policy by recognising Jerusalem as Israel’s capital.
“It’s the right thing to do,” a smiling Mr Netanyahu told the jubilant crowd at a reception in Jerusalem late on Sunday.
Monday’s opening was attended by Mr Trump’s daughter Ivanka and his son-in-law Jared Kushner, who both serve as White House advisers.
Mr Kushner leads the Trump Middle East team.