The rallies were organised by opposition and right-wing Islamist groups in major cities of the nuclear-armed country of 167 million people, where opposition to the government's US alliance is rampant.
In Karachi, the port city used by the United States to ship supplies to troops fighting in Afghanistan, more than 700 people gathered outside the US consulate, an AFP photographer said.
They shouted: "down with America, stay away Americans, Pakistan is ours, we stand shoulder-to-shoulder with our army", while Pakistani riot police were deployed near the consulate.
Outside the press club in Karachi, dozens of political activists burnt an effigy of President Obama, an AFP photographer added.
In the central city of Multan, more than 300 activists loyal to the former prime minister Nawaz Sharif, as well as local traders took to the streets, burning US and NATO flags.
They carried placards and banners, and shouted: "down with America," "down with NATO," "Yankees go back", "vacate Afghanistan and Pakistan" and "stop drone attacks" -- a reference to a CIA drone war against Islamist militants.
Speaking at the rally, opposition lawmaker Javed Hashmi demanded that the government end its alliance in the US-led "war on terror".
In Islamabad, at least 200 activists of the radical Jamaat-e-Islami (JI) party held a rally in the middle-class I-10 neighbourhood.
"We strongly condemn the attack and the killing of our soldiers," local JI chief Mian Aslam told the rally in reference to the air strike early Saturday, as protestors chanted "Pakistan is America's graveyard."
Pakistan has reacted with fury over the killings, and has called the attack by NATO helicopters and fighter jets on two military posts close to the Afghan border "unprovoked".
In response, Islamabad has sealed its Afghan border to NATO supply convoys and is reviewing its alliance with the United States and NATO, mulling whether to boycott a key international conference on Afghanistan next month.