At least 41 Palestinians were wounded and an Israeli police officer was shot on Saturday as Gazans rallied along the border, officials said.
Twenty-two children were among those hurt, including a 13-year-old boy who was critically wounded, the Gaza Health Ministry said.
Medics carried injured people away from the border east of Gaza city, where some Palestinians burnt tyres and threw stones at Israeli forces stationed across the fence.
The ministry said 27 people were injured in the lower body, without detailing the causes.
The Israeli military said a border police officer was shot from Gazan territory and flown to hospital.
Soldiers used live fire as “hundreds of rioters” approached the fence, with some throwing explosive devices at officers, the military said.
The border violence recalls the “March of Return” rallies in which 214 Gazans were killed, according to UN data, and more than 8,000 others suffered gunshot wounds.
Those protests were launched in 2018, more than a decade after Israel imposed a blockade on the Palestinian enclave, and ended the following year.
The latest rally comes three months into a ceasefire between Israel and Gaza rulers Hamas, which came into force in May after 11 days of fighting. It was the fourth war the two sides have fought since 2007.
The first rocket since the May conflict was launched from Gaza on Monday, although unusually it was not met with Israeli retaliatory strikes.
The incident came before Israel reaching a deal with Qatar to resume its money transfers to thousands of impoverished Gazans, which ended in May.
The UN is set to act as an intermediary under the new agreement, which replaces the earlier system of millions of dollars in cash being taken into Gaza in suitcases.