Iraqi Prime Minister Adel Abdul Mahdi said on Friday he would present his resignation to parliament so lawmakers could choose a new government, according to a statement from his office.
The announcement came after weeks of anti-government unrest in which security forces have killed around 400 mostly peaceful demonstrators and the country has careered towards a serious escalation of violence.
Abdul Mahdi's decision came in response to a call for a change of leadership on Friday by Iraq's top Shi'ite Muslim cleric Grand Ayatollah Ali al-Sistani, the statement said.
"In response to this call, and in order to facilitate it as quickly as possible, I will present to parliament a demand (to accept) my resignation from the leadership of the current government," said the statement, signed by Abdul Mahdi.
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The statement did not specify when he would tender his resignation. Parliament is due to convene on Sunday.
The death toll in Iraq from weeks of anti-government unrest rose on Friday to at least 408 people killed, mostly unarmed protesters, a Reuters count based on police and medical sources showed.
Several people died of wounds sustained in clashes on Thursday with security forces in the southern city of Nassiriya, hospital sources said, bringing the number of people killed there to at least 46 and the total nationwide to 408 since October 1.
The burning of Iran's consulate in the holy city of Najaf on Wednesday escalated violence and drew a brutal response from security forces who shot dead more than 60 people nationwide on Thursday.
The unrest is Iraq's biggest crisis for years. It pits protesters from Shi'ite heartlands in Baghdad and the south against a corrupt Shi'ite-dominated ruling elite seen as pawns of Iran.
'Chaos and infighting'
Iraq's current political class is drawn mainly from powerful Shi'ite politicians, clerics and paramilitary leaders including many who lived in exile before a U.S.-led invasion overthrew Sunni dictator Saddam Hussein in 2003.
Sistani, who only weighs in on politics in times of crisis and wields huge influence over public opinion, on Friday warned against an explosion of civil strife and tyranny. He urged government forces to stop killing protests and protesters themselves to reject all violence.
The government "appears to have been unable to deal with the events of the past two months ... parliament, from which the current government emerged, must reconsider its choices and do what's in the interest of Iraq," a representative of Sistani said in a televised sermon.
Protesters "must not allow peaceful demonstrations to be turned into attacks on property or people," he said.
Clashes between protesters and security forces broke out early on Friday in Nassiriya killing three people and wounding several others, hospital sources said.
Iraq's "enemies and their apparatuses are trying to sow chaos and infighting to return the country to the age of dictatorship ... everyone must work together to thwart that opportunity," Sistani said, without elaborating.