TTP have increasingly taken shelter on the Afghan side of the border after an army crackdown in their homeland, Pakistan officials say, although Afghanistan denies harbouring them.
The unmanned US aircraft targeted a car carrying Qari Mohammad Yasin, also known as Ustad Aslam, on Sunday in the southwestern Afghan province of Paktika bordering Pakistan, Pakistani intelligence sources said.
The attack killed Yasin, who specialised in training suicide bombers, and three other militants, added the officials, who declined to be identified as they are not allowed to talk to the media.
A US military spokesman in Kabul said US forces had conducted a drone strike in Paktika on Sunday but he declined to provide details, citing operational security reasons.
Pakistan's Counter-Terrorism Department had offered a bounty of 2 million rupees ($19,000) for Yasin, saying he was involved in the 2009 bus attack in the northeastern city of Lahore.
Confirmation of the death came from Ali bin Sufyan, spokesman for a Lashkar-e-Jhangvi offshoot, Al Alami, which has cooperated with Islamic State militants in the past.