More than 10,000 people were protesting when soldiers shot live ammunition and tear gas into crowds, Reuters reported.
Israel said the demonstrations – held to demand Palestinian refugees be allowed to return to their former homes in Israel – had turned violent.
The deaths, on Friday, came just hours after the United Nations human rights chief criticised the country for using “excessive force” during a spring of unrest along the 25-mile border.
Some 41 Palestinians have been killed and more than 5,000 wounded since six weeks of announced protests began on 30 March. Zeid Ra’ad Al Hussein, the UN high commissioner for human rights, called the loss of life deplorable.
The identities of those killed in the latest trouble have not yet been revealed. But among those injured were four medical staff and six journalists, the Palestinian Health Ministry reported.
The Israeli military said soldiers fired because the protests had turned into “riots”.
It said several Palestinians were attempting to cross by force and troops “had operated in accordance with the rules of engagement”, adding that protesters had hurled stones and rolled burning tires during the incident.
Others cleared away barbed wire which Israeli troops had placed in Gaza territory overnight in a bid to create a buffer zone.
Speaking before the latest trouble, Israel’s UN envoy, Danny Danon, told the Security Council that Hamas was responsible for Palestinian casualties and that it was using innocent Palestinian women and children as human shields.
“The terrorists are hiding while allowing, even hoping, for their people to die. This is evil in its purest form,” he said.
Hamas official Mushir Al-Masri said the claims were an “attempt to escape responsibility and to cover up for the execution of unarmed children and people by occupation soldiers".
Named the Great March of Return, the protests revive a longstanding demand for the right of return of Palestinian refugees to towns and villages which their families fled from when the state of Israel was created in 1948.
The Independent
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