Angry demonstrators armed with clubs and sticks set fire to and ransacked two cinemas in the conservative, northwestern city of Peshawar, where at least 15 people were wounded by gun shots, tear gas and stone throwers, said the Lady Reading Hospital.
A driver working for a private TV station was critically wounded and on a ventilator, said the hospital chief, Doctor Mukhtar Khan. His employer had earlier announced his death.
The violence came as Western missions across the Islamic world went on high alert, fearing further escalation of a 10-day violent backlash over the low-budget film "Innocence of Muslims" that has spread to at least 20 countries and left more than 30 people dead.
France, where a magazine this week published a series of cartoons mocking the Prophet Muhammad, has shut embassies, consulates, cultural centres and schools in 20 Muslim countries, fearing that the backlash will spread from US targets.
In Rawalpindi, the headquarters of Pakistan's powerful military, clashes broke out when scores of demonstrators pelted cars and police with stones, and burnt down a booth at a toll plaza, police official Mohammad Munir said.
An AFP reporter said police fired tear gas and live rounds into the air in a bid to disperse stone throwers and hundreds of protesters at the entry point to the capital Islamabad, which was blocked off by shipping containers.
But in the capital itself, protests were peaceful as hundreds demonstrated outside the five-star Serena Hotel, where the road to the heavily guarded diplomatic enclave was sealed off, shouting "Americans are dogs" and "Friends of America are traitors".
The government had declared Friday a holiday and "day of love for the prophet", calling for only peaceful protests and shutting down mobile telephone networks in an apparent bid to prevent Taliban and Al-Qaeda-linked extremists from carrying out bomb attacks.
Shops, markets and petrol stations shut down en masse, shuttering windows and erecting barriers in an unprecedented closure.
"It is our collective responsibility to protest peacefully without causing harm or damage to life or property," said Prime Minister Raja Pervez Ashraf.
But Friday was the second consecutive day of violence in Pakistan, after 5,000 angry protesters clashed with police and tried to storm Islamabad's diplomatic enclave.
Police used tear gas and live rounds to disperse the crowd in clashes that wounded dozens of officers and saw a police post burnt to the ground before the army was eventually called in.
Washington has warned citizens not to travel to Pakistan and spent $70,000 to air adverts on Pakistani television disassociating the US government from the film.
In Indonesia, the world's most populous Muslim nation, dozens torched an American flag outside the US consulate in Medan, and in the city of Surabaya, protesters chanted "crush America, crush France" outside the French consulate.
Demonstrators also scuffled with several hundred police in riot gear outside a McDonalds restaurant in Surabaya over the crudely made film believed to have made by extremist Christians in the United States.
In Malaysia, about 3,000 Muslims marched on the US embassy, burning an American flag topped with the Jewish Star of David in an otherwise peaceful protest.
In the Arab world authorities were also braced for demonstrations, with an Islamist militia in Libya's second city Benghazi calling for protests and demonstrations planned in Lebanon and the occupied West Bank.
US interests last week bore the brunt of protests against the amateur film, which depicts Muhammad as a thuggish sexual deviant.
But France has found itself in the firing line after satirical weekly Charlie Hebdo this week printed cartoons caricaturing the founder of Islam.
Its interior ministry says it will deny all requests to protest against the film after a demonstration last weekend near the US embassy in Paris turned violent, but news of the cartoons has appeared slow to filter into Islamic countries.
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 condemned Charlie Hebdo for publishing "insulting" images.
The magazine'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 United States is still investigating a deadly attack on one of its consulates in Libya on September 11th that left four Americans dead, including the ambassador.
The White House says FBI investigators suspect that Al-Qaeda may have been linked to the attack on the Benghazi compound, but it remains unclear whether it was a pre-planned assault or whether it sprang out of a protest against the film.