A local official said the compound that was hit belonged to Tariq Khan, who was described as a "facilitator of the Taliban".
Amir Shah, a resident of Waziristan, said drones were still flying over the area several hours after the attack.
With violence intensifying in Afghanistan, the US has launched more drone attacks on the Pakistani side of the border to destroy what it describes as "safe havens" for anti-government fighters.
The Pakistani government has protested to Washington against the drone strikes, saying they violated its territorial sovereignty.
But the US has kept up with its aerial attacks, accusing Islamabad of not doing enough to crack down on fighters who cross the border to attack US and Nato troops in Afghanistan.
Hundreds of Taliban and al-Qaeda fighters sought refuge in Pakistan's northwest tribal region after the US-led invasion of Afghanistan toppled the Taliban regime in late 2001.