The strike took place in Datta Khel town, 25 kilometres (15 miles) west of Miranshah, the main town in North Waziristan tribal district, which borders Afghanistan and is a stronghold of al Qaeda-linked Taliban militants.
"A US drone fired three missiles at a militant compound in Datta Khel. Five militants were killed in this attack," one intelligence official told AFP.
A security official in northwestern Peshawar city told AFP a militant compound had been targeted.
"We are not clear about the identities of the militants," he said.
The US drones, which operate with the tacit consent of Islamabad but fuel anti-US sentiment throughout the country, have mounted increasing attacks lately, pummeling the area believed to hide key Taliban-linked militants.
Missile attacks doubled in the area last year as the covert campaign was stepped up, with more than 100 drone strikes killing over 670 people in 2010 compared with 45 strikes that killed 420 in 2009, according to an AFP tally.
The last strike was on Monday when at least three militants were killed, according to security officials, in a US missile strike on a vehicle in a tribal town near the Afghan border.
Most have been concentrated in North Waziristan, where the United States wants the Pakistan military to launch a ground offensive as soon as possible.
Despite pressure from Washington, Pakistan has stalled on launching such an offensive in North Waziristan, saying its troops are already overstretched.
Wednesday's attack was launched hours before a Pakistani court is scheduled to resume the hearing of a CIA contractor in a double murder case that has ruptured relations between the United States and its wary nuclear-armed ally.
The hearing in the murder case against American Raymond Davis is due to take place in Kot Lakhpat jail in Lahore, where he is being held, as US authorities continue to press for his release on grounds of diplomatic immunity.
The United States does not confirm the drone attacks, but its military and the Central Intelligence Agency (CIA) operating in Afghanistan are the only forces that deploy them in the region.
The missile strikes cause widespread resentment among the Pakistani public, who see military action on their soil as a breach of national sovereignty.
But Islamabad tacitly cooperates with the bombing campaign, which US officials say has severely weakened al Qaeda's leadership and killed high-value targets including the former Pakistani Taliban chief Baitullah Mehsud.
US officials say Pakistan-based militants are helping to escalate the war in Afghanistan, putting up a deadly fight against 140,000 US-led Nato troops there and seeking to bring down the Western-backed government in Kabul.
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