The protests began in Karachi early on Friday morning
The clashes erupted as militants attacked an American fast-food outlet after spilling out of the city's mosques on the Muslim day of prayer.
Authorities have imposed a security clampdown across Pakistan to prevent violent protests against the US-led air strikes on Afghanistan.
Massive anti-US demonstrations were held in other areas of the world, including Indonesia, Malaysia, Bangladesh, Iran, and the Palestinian territories.
Protesters burned US and UK flags in Indonesia's capital Jakarta, and thousands of demonstrators in Malaysia were dispersed by water cannons. In the Gaza Strip, Palestinian police barred journalists and photographers from covering a planned demonstration by the militant group Islamic Jihad.
Pakistan clashes
Police and paramilitary troops in Karachi used tear gas to disperse some 3,000 demonstrators, who torched buses and cars and hurled stones.
The Reuters news agency said shots were fired from the crowd and police returned warning volleys of live ammunition into the air.
In contrast, the BBC's Daniel Lak said rallies following Friday prayers in the western city of Quetta dispersed peacefully, despite strong anti-US rhetoric.
Thousands of Muslim radicals reportedly streamed into the city, which was rocked by violence after the initial air strikes, leaving at least four people dead.
In anticipation of violence on Friday, the first Muslim day of prayer since the military action began, regular army troops and crack paramilitary units had been deployed in Quetta and in other cities.
Hundreds of soldiers were patrolling Quetta in large trucks and jeeps with roof-mounted machine guns in what is known in the Pakistan military as a "flag march", designed to send the message that the army is on guard against trouble.
'Mosques sacrosanct'
Pakistani President Pervez Musharraf told a meeting of provincial officials that the whole country wanted action against those who threatened peace.
He said that prayer meetings at mosques would not be allowed to foment unrest.
"These are places of worship, sacrosanct, to teach peace and tolerance in society," he said.
Security is also heavy around an air base in Jacobabad, one of two bases being used by American forces.
Barbed wire rings the air base and roads leading to it have been blocked.
"I have been stopped five times by soldiers," said one man. "You can't go anywhere near the airport."
'Quit'
In Peshawar, close to the Afghan border, several thousand protestors took to the streets in a peaceful protest against the US-led strikes.
The Associated Press news agency reported that armoured personnel carriers parked on corners and heavily armed soldiers lined the streets.
But there were no reports of violence.
Speaking in Peshawar, the leader of Pakistan's largest Islamic party called for the resignation of President Musharraf.
"Musharraf has violated his constitutional limits and has no justification to stay in power," Qazi Hussain Ahmed of the Jamaat-i-Islami party said. "He should resign immediately or else we will lay a siege on Islamabad," he said.
Correspondents say the authorities are taking no chances, especially with President Musharraf's potentially controversial moves to sideline senior army officers linked to Islamist political movements and the Taleban.