Twenty-four people, including nine children, have died in Gaza, the enclave's health ministry has announced, following all-night airstrikes from the Israeli military, which accused Palestinian militants of launching more than 200 rockets.
After weeks of intense violence in Jerusalem, Hamas, the Islamist group that rules inside Gaza, fired a barrage of rockets towards the holy city on Monday evening, believed to be the first time it had targeted the city in more than seven years.
In Gaza, health officials said seven members of a single family, including three children, had died in an explosion. It was not clear if the blast was caused by an Israeli airstrike or rocket that landed short.
Israel's military said it had killed 15 Hamas "operatives" and a Hamas battalion commander. Israeli medics reported six Israeli civilians were hurt by rocket fire, including those wounded from broken glass and shrapnel.
In recent weeks, a sharp escalation in anger has mounted around Israel's half-century occupation and its ever-deepening military grip over Palestinian life. In Jerusalem, hundreds of Palestinians have been wounded in near-nightly protests that ramped up over the weekend and spread to other areas of Israel and the occupied West Bank.
Israeli police have responded with stun grenades and rubber-coated bullets. On Monday morning, despite calls for calm from the US, Europe and elsewhere, officers riot gear stormed into the al-Aqsa mosque - the third holiest site in Islam - and faced off with worshippers. Hamas threatened action that day and began firing rockets on Monday evening.
Speaking after the first Gaza rockets were launched, the Israeli prime minister, Benjamin Netanyahu, said militants had "crossed a red line", adding: "Israel will respond with great force".
In a statement issued early on Tuesday, the Hamas leader Ismail Haniyeh said the rocket attacks would continue until Israel stopped "all scenes of terrorism and aggression in Jerusalem and al-Aqsa mosque".
Israel and Hamas have fought three wars. However, those wars were largely seen as a failure for both sides, with Hamas still in power and Israel continuing to maintain a crippling blockade.
Instead of full-scale conflict, the past few years have seen the enemies engage in regular on-off battles just shy of war. After each round, both sides claim they have scored points over the other and then an uneasy status quo is restored.
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Netanyahu has sought to show Israelis that he can keep them safe by not letting the violence spiral while also batting away criticism from his political partners on the far right, who accuse him of a tacit alliance with Hamas and an unwillingness to use greater force.
Israel's longest-serving leader is facing an especially precarious moment, with the 71-year-old's personal freedom at stake while under criminal corruption charges and his political future also hanging in the balance.
Last week, the opposition leader, Yair Lapid, was tasked with forming a government after Netanyahu failed to do so, leaving the prime minister facing a fresh challenge.
One prominent Israeli columnist, Ben Caspit, wrote on Tuesday that the recent violence may play in Netanyahu's favour as Lapid has been attempting to negotiate a deal with an Arab party in Israel, called the United Arab List, to form a government. With such high tensions, those negotiations appear in doubt.
"It's not certain Netanyahu himself is shedding any tears," wrote Caspit. "At the end of the day, Netanyahu's strategic alliance with Hamas has proven its worth. Not for Israel's benefit, but for Netanyahu's."
Jerusalem has long been the centre of the Israeli-Palestinian crisis, with its religious sites revered by Christians, Jews and Muslims. The al-Aqsa mosque is built on a compound that is the holiest site in Judaism, known to Jews as the Temple Mount.
Palestinians have complained of what they say are unnecessarily severe restrictions on nightly gatherings during the Muslim holy month of Ramadan.
Related: Israeli police storm al-Aqsa mosque ahead of Jerusalem Day march
Meanwhile, anger had been mounting for weeks among Palestinians around an Israeli court case on whether Israeli authorities are able to evict dozens of Palestinians from a majority-Arab Jerusalem neighbourhood and give their homes to Jewish settlers.
That ruling, due on Monday, was delayed but a provocative annual parade by thousands of Israeli nationalists in the city went ahead the same day. Jerusalem Day celebrate Israel's capture of the entire city, including the Old City and Palestinian neighbourhoods, from Jordanian forces in 1967.
Senior church leaders in Jerusalem criticised the "coordinated provocation of rightwing radical groups" that have contributed to violence in the city.
In a joint statement, the 13 patriarchs and heads of churches of various Christian denominations said events over recent days "violate the sanctity" of Jerusalem as a holy city, undermined the safety of worshippers. They called for intervention by the international community "to put an end to these provocative actions".
The Patriarch of Jerusalem, Theophilos III, said: "Jerusalem is holy to three religions, and believers of all these religions must be respected and enjoy freedom to observe their customs and traditions without fear or intimidation."
Anita Delhaas, the chief executive of the International Community of the Holy Sepulchre, said: "For too long hateful ideologies have been allowed to go unchecked, and the result is what we are witnessing in Jerusalem. Frequent attacks on holy sites, threats and intimidation of worshippers, and mob behaviour in the city's streets reflect alarming intolerance towards other religious communities."
Harriet Sherwood and the Associated Press contributed to this report