The gunmen opened fire at Bhittani's vehicle near Darga Mandi at Ghulam Khan area, security sources said. The Tehrik-e-Taliban Pakistan (TTP) commander and the others were killed instantly.
Bhittani carried a bounty of Rs 1 crore on his head and was among the 20 most wanted Taliban commanders. Geo News reported he had survived five previous attempts on his life.
Prior to joining the Taliban, Bhittani had been part of the Harkat-ul-Mujahideen and had fought in Jammu and Kashmir, the channel reported.
No group claimed responsibility for the killings.
Also Read
Bhittani had served as acting chief of the TTP after Hakimullah Mehsud was killed by a US drone last year. He also headed the Taliban's supreme 'shura' or council.
He belonged to the Bethni tribe of South Waziristan. The Bhethni tribesmen live in Jandola area of South Waziristan Agency and in Tank district of Khyber-Pakhtunkhwa province.
North Waziristan is one of seven semi-autonomous regions regions in Pakistan's tribal belt governed by tribal laws. US and Afghan officials say the region is a safe haven for Taliban and Al Qaeda elements.