JERUSALEM—Jerusalem suffered its bloodiest day yet Tuesday in the recent wave of unrest, with at least three Israelis killed as Palestinian attackers shot at a bus and another rammed a car into pedestrians.

The bus attack was the first assault with a gun in Jerusalem in the two-week-old upsurge of Palestinian violence.

The rising tide of violence, which has seen a series of stabbing attacks and protests, has raised fears of a full-scale third Palestinian intifada, or uprising.

READ: Palestinians and Israel forces clash in Jerusalem, West Bank

A Palestinian was also killed in clashes in the West Bank city of Bethlehem.

In the intifadas of 1987 to 1993 and 2000 to 2005, hundreds of people were killed in near daily Israel-Palestinian violence.

The US was swift to condemn the attacks and call for calm.

“I continue to urge all sides to take affirmative steps to restore calm and I will stay in very close touch with leaders in the region in the days ahead,” said US Secretary of State John Kerry.

“The United States condemns in the strongest terms possible the terrorist attacks against Israeli civilians,” he told reporters in Washington.

Tuesday’s attack on an east Jerusalem bus saw one Palestinian with a pistol and another wielding knives assault some 15 people, police said.

Two Israelis, including a 60-year-old were killed, and around 10 were wounded, medics and police said.

READ: Palestinian attacker stabs 2 in Jerusalem in latest violence

One attacker was shot dead and the other was wounded.

“I was in my house and I heard between 20 and 30 shots between the police and the terrorists,” an area resident said.

At around the same time, in an ultra-Orthodox Jewish area of the city, a Palestinian rammed a car into people at a bus stop and jumped out with a knife.

At least one person was killed and eight wounded, medics said. The attacker was shot and later died, police said.

All three assailants were from the east Jerusalem neighborhood of Jabel Mukaber, police said, but it was unclear if the attacks were coordinated.

A spokesman for Hamas, the Islamist movement that controls the Gaza Strip, called the attacks “heroic” and said the “intifada is intensifying.”

‘Day of rage’

The Jerusalem attacks came after a Palestinian stabbed and wounded a passer-by north of Tel Aviv before being overpowered by civilians.

Police said that attacker was a 22-year-old Palestinian from east Jerusalem and that he was hospitalized after residents severely beat him.

Initially limited to annexed east Jerusalem and the occupied West Bank, unrest has spread to Gaza, with Israeli troops killing nine Palestinians in border clashes in recent days.

Prime Minister Benjamin Netanyahu said Tuesday that Israel would use “all means” available to end Palestinian violence and that new security measures were planned.

Speaking to parliament, he warned Palestinian president Mahmud Abbas that he would hold him responsible if incitement led to a further deterioration.

Palestinians had called for a “day of rage” Tuesday and Arab Israelis called a general strike.

Violent protests took place in parts of both Gaza and the West Bank, including in Bethlehem and at a checkpoint near Ramallah where Israeli fire wounded at least one Palestinian.

A 28-year-old Palestinian was killed in Bethlehem, and Palestinian medics reported at least 15 Palestinians wounded by Israeli fire.

Funerals of Palestinians killed in unrest or while allegedly carrying out attacks—as well as online videos of shootings—have fed anger.

‘Knife terror’

Palestine Liberation Organization secretary general Saeb Erakat said new petitions would be sent to the International Criminal Court against Israel, accusing it of “extrajudicial executions.”

More than 20 stabbing attacks have occurred in Israel, Jerusalem and the West Bank since October 3.

There has been one revenge attack, with a Jew stabbing and wounding two Arab Israelis and two Palestinians in the southern Israeli city of Dimona last week.

Seven Israelis have been killed along with about 30 Palestinians, including alleged attackers.

The assailants are usually youths who appear to be acting on their own.

Frustrated Palestinian youths have defied Abbas and an Israeli crackdown by staging violent protests in east Jerusalem and the West Bank.

Tuesday saw further unrest along the Israel-Gaza border when about 1,000 protesters threw stones and firebombs at a checkpoint.

Israel’s army also said “shots were fired at a military vehicle along the security fence in the southern Gaza Strip.”

The violence began October 1, when an alleged Hamas cell shot dead a Jewish settler couple in the West Bank in front of their children.

Those murders followed repeated clashes at Jerusalem’s flashpoint Al-Aqsa mosque compound in September between Israeli forces and Palestinian youths.

UN chief Ban Ki-moon urged Israel to carry out a “serious review” on whether its security is resorting to excessive force in the clashes.