Gaza's health ministry said 12 Palestinians were wounded.
Several thousand had gathered near the border, while smaller numbers of stone-throwing Palestinians were approaching the fence and seeking to damage it, with Israeli snipers positioned on the other side.
Larger crowds were expected to gather later in the day to protest the move of the US embassy in Israel from Tel Aviv to the disputed city of Jerusalem.
The embassy inauguration was due to occur at 4:00 pm (1300 GMT).
Fifty-four Palestinians have been killed by Israeli fire since protests and clashes began along the Gaza border on March 30.
The protests are calling for Palestinian refugees who fled or were expelled during the 1948 war surrounding Israel's creation to be allowed to return to their homes now inside Israel.
No Israelis have been wounded and the military has faced criticism over the use of live fire.
Israel says it only opens fire when necessary to stop infiltrations, attacks and damage to the border fence, while accusing Hamas, the Islamist movement that runs the blockaded Gaza Strip, of seeking to use the protests as cover to carry out violence
Bilal Fasayfes, 31, was getting on a free bus to the border with his wife and two children in the southern Gazan city of Khan Yunis.
"If half the people die we won't care," he said.
"We will keep going so the other half can live with dignity."
Also in Khan Yunis, groups of masked young men, some carrying wooden bats, walked between shops forcing them to close to respect a general strike.
Muataz al-Najjar, 18, who was wounded four times in the last seven weeks, once from a bullet and the others from gas cannisters, said he hoped to break through the fence.
"We will return and the move of the embassy from Tel Aviv will be prevented."
At Shifa Hospital, where doctors say they are running low on crucial supplies and being forced to discharge patients early to make space for the next wave, a large tent was established outside in front of the emergency room.
At mosques in the cities, large speakers were set up that are expected to broadcast messages encouraging people to go to the border.
Faris Abu Hajaras, 50, said his family was from Jaffa, now within Israel, but he had never been there. He is a builder but said Israel's blockade of the strip meant there was no work.
"We will stay peaceful with our hands like this," he said, lifting them to the sky. "But death comes from God. Maybe you and I are walking together and you get shot in the head and I will be fine."
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