Geo News, quoting its officials sources, put the death toll from the strike at 18.
Dawn reported the strike late Tuesday night or early Wednesday targeted a house near a bazaar in the Sirai Darpakhel area of Miramshah, the administrative headquarters of North Waziristan.
The tribal region is seen by U.S. military officials as a haven for Taliban and other militant groups to launch attacks against coalition forces in neighboring Afghanistan.
Dawn, quoting Pakistani intelligence sources, said four missiles were fired at the house, leaving 17 dead and two more injured. The report gave no details about those killed.
Geo News said the drone attacked a residential compound and a vehicle in the area, killing 18 people.
The drone attack, based on the number of reported casualties, would be a major one and comes at a time when Pakistan has a new government led by Prime Minister Nawaz Sharif. The Sharif government strongly opposes the drone program, saying it violates Pakistan's sovereignty and only helps fan anti-American sentiments.
Last May, a drone strike killed Waliur Rehman Mehsud, leader of the Pakistani Taliban called Tehrik-e-Taliban Pakistan.
Sharif, who became prime minister after his party won elections in May, has said he wants to negotiate with the Pakistani Taliban.
Also in May, in a speech on counter-terrorism, U.S. President Barack Obama announced a new drone policy to limit civilian casualties, although the program has been a major factor in crippling al-Qaida and other militants.
Jessica Simpson shares three-way kiss with friends in photo
Susan Sarandon 'very excited' about daughter's pregnancy