Thousands of Pakistanis attempted to storm Islamabad's diplomatic enclave, as anger mounted across the Muslim world over perceived Western insults to the Prophet Mohammed.
Similar demonstrations took place in several countries, as the anger that erupted when a US group of Christian extremists released a crudely-made film attacking Mohammed was further stoked by caricatures in a French magazine.
In a foretaste of what might come when tens of millions of Muslims leave their mosques on Friday after weekly prayers, crowds in Nigeria, Iran and Afghanistan chanted: "Death to France. Death to America. Death to Israel."
In Islamabad, police fired teargas and live rounds as they defended the heavily-guarded diplomatic district, home to Western embassies including the US, British and French missions, against mobs of club-wielding protesters.
Dozens of officers were wounded and a police post burnt to the ground before army troops were eventually called in to disperse the protesters, who had breached a wall of shipping containers designed to hold them back.
Western missions are on high alert as the United States investigates a deadly attack on one of its consulates in Libya, and ahead of Friday's prayers, which are often a prelude to protest in the Muslim world.
The Pakistani government called an impromptu public holiday to let people protest, saying Friday had been designated a "day of love for the prophet," but calling on people to protest the film peacefully.
All major political parties and religious groups in Pakistan have announced protests, as have many trade and transport organisations, and large crowds are expected to turn out after Friday prayers.
The State Department meanwhile bought time on several Pakistani networks to air advertisements in Urdu in a bid to dissociate the US government from the inflammatory film, a US official said.
The White House confirmed that FBI investigators suspected that Al-Qaeda may have been linked to the September 11 attack in the Benghazi compound, which left four US officials dead, including the ambassador to Libya.
It is not yet clear whether the attack by armed militants sprang out of the protest movement against the privately-produced film or whether it was a pre-planned assault by an organised Islamist faction.
But US President Barack Obama's spokesman called the killings a "terrorist attack" and said officials were probing reports that the militants could have links to Al-Qaeda or its North African offshoot.
Separately, US Secretary of State Hillary Clinton announced that a senior panel would be appointed to review security in the wake of the killings. She was also to brief lawmakers on the investigation into the attack.
US interests bore the brunt of the first wave of protests, after Christian activists released a trailer for an amateurish movie, "The Innocence of Muslims", depicting the Prophet Mohammed as a thuggish sexual deviant.
But this week France also found itself in the firing line after the French satirical weekly Charlie Hebdo printed a batch of cartoons caricaturing the founder of Islam, including two showing him naked.
French authorities banned a demonstration planned for Saturday in front of Paris' Grand Mosque, and will close diplomatic missions, cultural centres and French schools in around 20 Muslim countries on Friday.
The French interior ministry has said it will deny all requests for permits to protest the film after a demonstration last weekend near the US embassy in Paris turned violent.
Leaders of France's Muslim community -- the largest in western Europe -- said an appeal for calm would be read in mosques across the country on Friday but also condemned Charlie Hebdo for publishing "insulting" images.
Charlie Hebdo's editor, Stephane Charbonnier, mocked those angered by the cartoons as "ridiculous clowns" and accused the government of pandering to them by criticising the magazine for being provocative.
The US State Department has warned its citizens to avoid travel to Pakistan, and Washington has boosted security at its diplomatic missions worldwide.