Thousands demonstrated in Karachi on Sunday to demand an immediate end to US missile strikes in Pakistan's lawless tribal areas and urge the blocking of NATO supplies passing through the country.

Activists from the Tehreek-e-Insaf (Movement for Justice) continued a two-day sit-in outside the city's Arabian Sea port, urging the government to end its cooperation with Washington's "war on terror".

"It is not Pakistan's war, this is America's war. This war has killed thousands of innocent Pakistanis, women and children," the group's leader and former cricketer Imran Khan told the gathering of around 7,000 supporters.

Karachi is Pakistan's economic hub, home to its stock exchange and a lifeline for a depressed economy wilting under inflation and stagnating foreign investment.

The city, the country's largest, is important to logistical support for NATO forces fighting against Taliban militants in Afghanistan.

"There was not a single Taliban militant in Pakistan before 9/11 but since we joined this war, we are facing acts of terrorism, bombing and drone strikes," Khan said.

The demonstrators chanted anti-US slogans and carried banners and placards reading "Death for America" and "Stop drone strikes in Pakistan".

Khan said the US drone strikes were creating "suicide bombing factories" and urged the government to stop taking foreign aid.

"These attacks are against Pakistan's interests. I ask the government to stop NATO supplies via Pakistan, but I am sure they can't, because these shame-proof rulers are getting dollars," he said.

NATO supply trucks, oil tankers and equipment required by coalition troops in Afghanistan are shipped through Pakistan, although US troops increasingly use alternative routes through central Asia.

The US drone strikes are deeply unpopular among the Pakistani public, who see foreign military action on Pakistani soil as a violation of national sovereignty.

Pakistan has officially protested to the United States that the strikes violate its sovereignty, although some officials have said there is a tacit understanding between the two militaries allowing such action.