The commander, Maulvi Nazir, fought American forces in Afghanistan but had a truce with the Pakistani military. He was among nine people killed in a missile strike on a house in the village of Angoor Adda in the South Waziristan tribal region near the border with Afghanistan.
At least four people were killed in a separate drone strike later near Mir Ali, the main town of the North Waziristan tribal region.America's use of drones against militants in Pakistan has increased substantially under President Barack Obama and the programme has killed a number of top militant commanders over the past year.
But the drone strikes are extremely contentious in Pakistan, seen as an infringement on the country's sovereignty. And while the US maintains that it targets militants, many Pakistanis complain that innocent civilians have also been killed.
Nazir's killing could cause even more friction in the already tense relations between Washington and Islamabad. Pakistan is believed to have struck a non-aggression pact with Nazir ahead of its 2009 military operation against militants in South Waziristan.
Fighters under Nazir's command focused their attacks on American forces in neighbouring Afghanistan. But many in Pakistan's military viewed Nazir and militant chiefs like him as "good Taliban," meaning they focus attacks only on foreign forces in Afghanistan, keeping domestic peace by not attacking Pakistani targets.
Nazir outraged many Pakistanis in June when he announced that he would not allow any polio vaccinations in territory under his control until the US stops drone attacks in the region.
Pakistan is one of three countries where polio is still endemic. Nine workers helping in anti-polio vaccination campaigns were killed last month by militant gunmen and the killings this week of five female teachers and two aid workers may also have been linked to their work on the polio campaigns.
Residents in Angoor Adda and Wana, the biggest town in South Waziristan, said mosque loudspeakers announced Nazir's death. One resident, Ajaz Khan, said 5,000 to 10,000 people attended the funeral of Nazir and six other people in Angoor Adda. A resident who attended the funeral said Nazir's body was badly burned and his face unrecognisable.
Nazir was active in many parts of Afghanistan and had close ties with Arab members of al Qaida as well as the Afghan Taliban, said Mansur Mahsud, the head of the Islamabad-based FATA Research Centre, which studies the tribal regions."His death is a great blow to the Afghan Taliban," he said.