Bloodshed broke out on Sunday as Palestinian refugees across the region marched on Israel's borders in a mass show of mourning over the 1948 creation of the Jewish state.
Israeli gunfire killed at least two people on the border with Lebanon as thousands of mainly Palestinian refugees demonstrated along the tense frontier, according to a Lebanese security official.
And Israel's military said dozens of people were wounded when the army opened fire fire at "thousands" of protesters crossing from Syria into the Israeli-annexed Golan Heights.
Among numerous rallies and demonstrations to mark the anniversary, clashes also broke out between stone-throwing Palestinian youths and Israeli security forces, leaving nearly 80 injured.
In northern Gaza, more than 1,000 Palestinians marched on the Erez border crossing, prompting troops to open fire, wounding at least 61 people, most of them minors.
Hundreds of miles to the north, the Israeli Army said thousands of protesters broke into the annexed Golan from the Syrian-held side of the disputed plateau, prompting troops to fire off live rounds and tear gas.
Medical sources said between 10 and 20 people were wounded in what the army branded a "very serious and violent" incident. Four protesters died, according to media reports, but there was no immediate confirmation from officials.
Violence also swept the Lebanese border where thousands of Palestinian refugees were bussed to the border to protest the anniversary, although Israeli defence sources gave no immediate reports of gunfire.
In the occupied Palestinian territories, Israeli gunfire wounded at least 78 Palestinians in a series of clashes, medics said.
The vast majority were wounded in Gaza, where troops opened fire as more than 1,000 people marched on the towering concrete border fence, chanting: "No to the occupation!" and "Revolution, revolution to liberate Palestine!"
Emergency services spokesman Adham Abu Selmiya said 61 people were wounded, including seven left in serious condition.
Further South, more than 5,000 demonstrators also held a mass rally in the Southern Gaza city of Rafah, which lies on the border with Egypt, an AFP correspondent said.
They waved Palestinian flags and held up huge replica wooden keys to homes they fled or were expelled from during the Arab-Israeli war which accompanied the creation of the Jewish state.
Since on Friday, Palestinians and Arab Israelis staged a series of events in the run-up to on Sunday's anniversary.
In the Southern city of Hebron, nine people were hit by rubber bullets fired by Israeli troops as an estimated 2,000 demonstrators held a protest, with clashes also reported in the nearby towns of Al-Arub, Beit Ummar and Bani Naim.
And eight Palestinians were hit by rubber bullets in heavy clashes near the Qalandiya crossing between the West Bank town of Ramallah and annexed east Jerusalem, where thousands gathered for a protest, medical sources said.
In Jerusalem, police arrested 13 people for disturbing the peace as clashes erupted in several locations across the eastern sector of the city, pitting stone-throwing youths against police and border police in riot gear.
In Tel Aviv, a truck driven by a 22-year-old Arab Israeli ploughed into a bus and at least four cars, killing one person and injuring another five with police investigating whether the driver had been acting on nationalist motives.
For two days, stone-throwing youths and police have been locked in clashes across east Jerusalem, which turned deadly on Friday when a 16-year-old boy was shot in the stomach.
He died early on Saturday, with a relative telling AFP he had been shot by a Jewish settler.
More than 760,000 Palestinians — estimated on Sunday to number 4.7 million with their descendants — were pushed into exile or driven out of their homes in the conflict that accompanied the Jewish state's foundation.
The violence came as Palestinians across the region marked the anniversary of the state's establishment in 1948, known in Arabic as the "nakba" or "catastrophe."
Israel celebrated the 63rd anniversary on Tuesday, in accordance with the Hebrew calendar.