The Palestinian Red Crescent said that 57 people were wounded, including 14 Palestinians taken to hospital, one of them in a serious condition, after police stormed the compound in Israeli-annexed east Jerusalem's Old City.
The clashes come after a month of deadly violence, as the Jewish festival of Passover overlaps with the holy Muslim fasting month of Ramadan.
The violence has sparked international fears of conflict, one year on since similar unrest led to an 11-day war between Israel and militants in Gaza.
This week, Palestinian groups in the Gaza Strip have fired rockets at Israel, which has responded by sending warplanes to strike the blockaded and impoverished territory.
"We are deeply concerned by the escalating violence in the occupied Palestinian territory and Israel over the past month," said Ravina Shamdasani, spokeswoman for the UN Office of the High Commissioner for Human Rights.
Tear Gas By Drone
Israeli police said Palestinians began hurling stones before dawn Friday towards the Western Wall, the holiest site where Jews can pray.
"Police forces used crowd dispersal means in order to stop the violence," said a statement, adding that one officer was wounded.
Al-Aqsa is Islam's third-holiest site, and the most sacred site in Judaism where it is known as the Temple Mount.
Police fired tear gas and rubber-tipped bullets at stone-throwing Palestinian youths, and later used drones to spray tear gas from the air, an AFP photographer said.
After midday prayers, some worshippers chanted "incitement" and tried to damage a security post, police said.
More than 200 people, mostly Palestinians, have been hurt in clashes in and around Al-Aqsa in the past week.
Palestinians have been outraged by massive Israeli police deployment and repeated visits by Jews to the holy site.
By long-standing convention, Jews are allowed to visit under certain conditions but are not allowed to pray there.
Palestinian worshipper Alaa al-Haddad said Israel was restricting access to Al-Aqsa, and that this had created "tensions that lead to clashes", with hundreds of people arrested in recent days.
"It's all because the occupation forces are regularly storming the holy Al-Aqsa mosque," Haddad said.
Gaza Rocket Fire
On Thursday, Arab ministers meeting in Jordan -- custodian of east Jerusalem's holy sites -- denounced "Israeli attacks and violations against worshippers" at Al-Aqsa, branding them "a blatant provocation to the feelings of Muslims everywhere".
On Friday, the United Nations' High Commissioner for Human Rights demanded a probe into the Israeli police actions.
"The use of force by Israeli police resulting in widespread injuries among worshippers and staff in and around the Al-Aqsa mosque compound must be promptly, impartially, independently and transparently investigated," Shamdasani said.
But Israeli Foreign Minister Yair Lapid, speaking on Thursday after meeting with US acting Assistant Secretary of State Yael Lempert, has contradicted Palestinian claims and insisted that Israel was "preserving and will continue to preserve the status quo on the Temple Mount".
The latest spike in violence, including four deadly attacks since March 22 inside Israel carried out by Palestinians and Israeli Arabs, have claimed 14 lives.
Over the same period, 24 Palestinians have been killed, including assailants who targeted Israelis, according to an AFP tally.
Among them is Ibrahim Labdy, 20, from Jenin, who died on Friday from wounds sustained during an Israeli raid on the city last week.
Violence has also surged in the Palestinian coastal enclave of the Gaza Strip, run by the Islamist movement Hamas, where crowds rallied on Friday in solidarity with those in Al-Aqsa.
On Thursday, Gaza militants and Israeli warplanes exchanged fire in the biggest escalation in months.
After a rocket fired by militants hit the garden of a house in southern Israel late Wednesday -- the first such attack since January -- Israel launched air strikes against Gaza.
The military said it had hit an underground rocket factory, prompting another volley of rockets from Gaza.
Hamas spokesman Fawzi Barhoum said the movement was "determined to continue the struggle... no matter the sacrifices".
The violence has proved a political headache for Israeli Prime Minster Naftali Bennett, who leads an ideologically divided coalition government.
After losing its one-seat majority in parliament earlier this month, the Raam party, drawn from the country's Arab minority, suspended its support for the coalition over clashes at Al-Aqsa.