Furious protesters targeted symbols of US influence in cities across the Muslim world, attacking embassies, schools and restaurants in retaliation for a film that mocks Islam.
At least six protesters died in Egypt, Tunisia, Lebanon and Sudan as local police battled to defend American missions from mobs of stone-throwers, and Washington deployed US Marines to protect its embassies in Libya and Yemen.
The protests broke out when Muslims emerged from mosques following weekly prayers to voice their anger at a crude film made in the United States by a right-wing Christian group that ridicules the Prophet Mohammed.
Clashes or demonstrations were reported from as far apart as Mauritania and Indonesia. Troops in Nigeria fired live rounds in the flashpoint city of Jos and Egyptian police fought street battles in downtown Cairo.
In the Sudanese capital Khartoum, guards on the roof of the US embassy fired warning shots as the compound was breached by protesters waving Islamic banners, after earlier ransacking parts of the British and German missions.
Tunisian demonstrators, meanwhile, set fire to several vehicles and an American school during a failed attack on the main embassy compound, and in Lebanon, 300 Islamists set fire to a branch of the US fast food chain KFC.
In Washington, President Barack Obama welcomed home the bodies of four US officials who were killed on Tuesday when armed militants stormed the consulate in Benghazi, cradle of last year's Western-backed Libyan revolution.
"Their sacrifice will never be forgotten, we will bring to justice those who took them from us. We will stand fast against the violence on our diplomatic missions," Obama said at Andrews Air Force Base.
The fighting brought foreign policy back to the heart of the debate in the US presidential race, and on Friday also clouded the start of Pope Benedict XVI's three-day visit to Lebanon to promote Muslim-Christian coexistence.
In much of the region, police from broadly pro-Western regimes attempted to contain the protests, but in Iran, crowds had official sanction to chant "Death to America" and "Death to Israel" in central Tehran.
In India, police arrested 86 protesters in Chennai and in Afghanistan the outrage whipped up by the film mixed with resentment at the ongoing Western military presence to feed large-scale street protests.
The eruption of violence posed a challenge for Obama, less than eight weeks before his re-election battle against Republican challenger Mitt Romney, who accused the incumbent of inviting violence through a weak and muddled stance.
In response, Obama has promised to show resolve and to stand by the fragile fledgling democracies of the Middle East, while deploying platoons of marines to vulnerable embassies and hunting the killers of the four envoys.
"Even as voices of suspicion and mistrust seek to divide countries and cultures from one another, the United States of America will never retreat from the world," Obama vowed, alongside the flag-draped coffins.
Secretary of State Hillary Clinton told relatives of the dead men -- US ambassador Chris Stevens, information officer Sean Smith and former Navy SEALs Tyrone Woods and Glen Doherty -- that the killings dishonored the Arab Spring.
"The people of Egypt, Libya, Yemen, and Tunisia did not trade the tyranny of a dictator for the tyranny of a mob," she said.
European Union foreign policy chief Catherine Ashton on Friday urged leaders in Arab and Muslim countries to "call immediately for peace and restraint," condemning the attacks on diplomatic missions.
US military and intelligence agencies have already launched a manhunt in Libya for the militants who staged the assault on the Benghazi consulate, with an FBI team on its way and drones criss-crossing North African skies.
"There's an intense focus," a US defense official told AFP.