Nearly 180 Palestinians were injured as Israeli forces fired rubber bullets, tear gas and stun grenades at hundreds of Palestinians attending night prayers at the compound.
The clashes took place on the International Quds Day, the last Friday of the holy Muslim fasting month of Ramadan.
The Palestine Red Crescent ambulance service said 88 of those wounded were taken to hospital, adding, one of them lost an eye, two suffered serious head wounds and two had their jaws fractured.
Dozens of worshipers were also arrested by the occupation forces, according to Wafa news agency.
In a televised statement, Palestinian President Mahmoud Abbas held the Tel Aviv regime fully responsible for the “dangerous developments and sinful attacks that are taking place in the Holy City, and for the consequences thereof," urging the United Nations Security Council to hold an urgent session on the issue.
Tensions have increased in the occupied West Bank during Ramadan, with nightly clashes in East Jerusalem al-Quds’ Sheikh Jarrah, which sits near the Old City's Damascus gate.
Numerous families face eviction in the Palestinian neighborhood due to illegal settlement expansion policies of the occupying regime.
On Friday, scuffles broke out near Sheikh Jarrah as Israeli forces used water cannon mounted on armored vehicles to disperse protesters.
Iran 'strongly condemns' Israeli raid
Iran’s Foreign Ministry spokesman Saeed Khatibzadeh said the Islamic Republic “strongly condemns” the Israeli raid on the al-Aqsa Mosque, the first Qiblah of Muslims (a place toward which Muslims pray), on the Quds Day.
"This war crime once again proved to the world the criminal nature of the illegitimate Zionist regime and the need for urgent international action to stop the violation of the most fundamental principles of international humanitarian law," he added.
"In addition to condemning this definite crime against humanity and offering condolences to the families of the martyrs of this incident and wishing a speedy recovery for the wounded, the Islamic Republic of Iran calls on the UN and other relevant international organizations to fulfill their decisive duty against the war crime.”
Khatibzadeh also noted that Iran “proudly stands by the heroic people of Palestine and calls on all world countries, especially Muslim states, to honor their historic task and stand by the Palestinian nation in the face of the Zionist aggressors.”