That unprecedented barrage of rockets, along with deadly Israeli airstrikes, have killed civilians caught in the crosshairs on both sides, while waves of Arab-Israeli street clashes are now rising within Israel itself -- a new threat of violence that could quickly worsen.
The Biden administration has consistently called on "both sides" to de-escalate, leading to criticism from American conservatives who accused Biden of not standing strongly enough with Israel and from American progressives who said the power dynamic is asymmetrical and Israel's response has been disproportionate.
Wading into those waters now is senior U.S. diplomat Hady Amr, who serves as deputy assistant secretary for Israeli and Palestinian affairs. Secretary of State Antony Blinken dispatched Amr to the region Wednesday to meet with Israeli and Palestinian officials and urge de-escalation.
The death toll in Gaza has risen to 65 Palestinians, including 16 children, while at least 365 have been wounded, including 86 children, according to the Associated Press, citing the local health ministry. On the Israeli side, seven have been killed by rocket fire, including two children, while dozens have been wounded, as Hamas' rockets overwhelm Israel's Iron Dome defense system.
Breaking his silence on the issue, Biden told reporters Wednesday, "My expectation and hope is that this will be closing down sooner than later."
A White House readout issued afterwards added that Biden "conveyed his unwavering support for Israel's security and for Israel's legitimate right to defend itself and its people, while protecting civilians." The brief statement made no mention of Palestinian civilian deaths or Israeli actions that helped to spark this round of clashes, like the potential evictions of Palestinians in East Jerusalem or the use of force against Muslims at the Temple Mount.
Earlier in the day, Blinken was more nuanced, condemning the barrage of rocket fire from Hamas, but adding that Israel has an "extra duty" to avoid civilian casualties and that Palestinians have a "right to safety and security."
He said that the U.S. is "deeply engaged across the board," including with Palestinian leadership and that the "most important thing now is for all sides to cease the violence, de-escalate and to try to move to calm."
To that end, he also spoke to Netanyahu Wednesday and "emphasized the need for Israelis and Palestinians to be able to live in safety and security, as well as enjoy equal measures of freedom, security, prosperity and democracy," his spokesperson said.
Netanyahu thanked Blinken "for the American support of Israel's right to self-defense, which the Secretary reiterated during the call," according to an Israeli readout. The embattled prime minister has so far rejected calls for a ceasefire, saying Hamas must pay a price and vowing to expand the Israeli offensive.
Prior to Biden's call, critics, including Republican lawmakers and his predecessor Donald Trump, accused Biden of pulling back U.S. support for Israel.
White House press secretary Jen Psaki said Tuesday that Biden has been briefed daily and added Wednesday that senior U.S. officials have had more than 25 "high-level calls and meetings" with officials from Israel, the Palestinian Authority and key regional countries, including Qatar, Jordan and Egypt.
On Tuesday night, Biden's national security adviser Jake Sullivan spoke to his Israeli counterpart Meir Ben Shabbat and to Egyptian officials, according to his spokesperson Emily Horne. Egypt historically has played the role of directly negotiating with Hamas, which the U.S. has designated a terrorist organization, and Sullivan and Egyptian officials "discussed steps to restore calm over the coming days and agreed to stay in close touch," according to Horne.
While the two countries have strong security relations, Egypt's Foreign Minister Sameh Shoukry said Tuesday that his government had tried to contact the Israeli Foreign Ministry, but had not received a response. Then on Wednesday, the two foreign ministers spoke.
Shoukry stressed "the need to stop Israeli attacks on Palestinian territories and the importance of working to spare the peoples of the region further escalation and any resorting to military means, stressing Egypt's keenness to stabilize the region on the basis of settling issues by diplomatic means and through negotiations."
While Biden seems reluctant to get involved, convincing Netanyahu to pull back may fall to the U.S. -- starting with Amr, who served in the Obama administration as deputy special envoy for Israeli-Palestinian negotiations. While he is a senior diplomat, he's also the administration's only top official on this issue right now. There's no U.S. ambassador to Israel, let alone a Biden nominee; no special envoy for Israeli-Palestinian issues, even as Biden has appointed several other envoys; and no U.S. consul general in East Jerusalem, a role that Trump dissolved but historically was the top liaison to Palestinian leadership.
"The Biden administration cannot ignore this conflict. In the first four months of this administration, it's very clear that this issue was not a priority ... but it is irresponsible to step away from engaging in a meaningful way," said Jeremy Ben-Ami, president of J Street, a liberal advocacy group. "It leaves the conflict unattended and contributes heavily to the escalating tensions that can explode as they precisely have in the last 48 hours into violence."
The State Department has denied that the administration hasn't been engaged, instead blaming the fact that neither Israeli nor Palestinian leadership has been willing to engage in peace negotiations.
"We're just not in a position to see meaningful progress, and our policy has recognized that," spokesperson Ned Price said Monday.
Price's comments have sparked some anger on the left, including from Democratic lawmakers including Reps. Rashida Tlaib, Jamaal Bowman and Ilhan Omar.
After he equivocated on issues like the Palestinians' right to defense and the asymmetrical levels of strength between the two sides, Omar, D-Minn., tweeted Monday, "This unsurprising response is devoid of empathy and concern for human suffering. He can't even condemn the killing of children."
Price later cited the early nature of reports and said the administration wouldn't speak until there was confirmation on the ground. But he and Blinken have changed their tone slightly to more vocally defend Palestinian civilians, even as they condemn Hamas' rocket attacks.
Asked about the proportionality of Israel's response Wednesday, Blinken said there was a "very clear and absolute distinction" between Hamas "targeting civilians and Israel's response defending itself." But he added that civilian casualties in Gaza have "a powerful impact, and I think Israel has an extra burden in trying to do everything it possibly can to avoid civilian casualties."
ABC News' Hatem Maher in Cairo and Ben Gittleson and Karen Travers at the White House contributed to this report.