Samiul's son, Hamidul Haq, said his father was alone in his bedroom when he was attacked by an assailant, who escaped undetected.
"My father has been martyred. He was alone at his home. His guard had gone out minutes before the attack and upon his return he saw my father in critical condition," he told reporters.
Police say Samiul, 81, was taken to a nearby hospital, where he died.
Yousaf Shah, Samiul's spokesman, told The Associated Press that neither the attacker nor their motive was yet known.
Soon after his death, scores of Samiul's supporters rioted, damaging shops and vehicles in Islamabad and Rawalpindi. Samiul's family appealed to his followers to remain peaceful.
A well-known religious scholar with a large following among radical Islamists, Samiul was the head of his faction of the Jamiat-e-Ulema Islam (JUI) party.
Samiul was a revered teacher with vast influence over Pakistan and Afghanistan's Taliban, many of whose leaders and commanders studied a strict interpretation of Islam at his Haqqani seminary, earning him the "father of the Taliban" title.
Sirajuddin Haqqani, the deputy leader of the Haqqani network, a US-designated terrorist organization, was one of the dozens of Taliban leaders who graduated from Haq's seminary, located in the conservative Khyber Pakhtunkhwa province on the border with Afghanistan.
In recent weeks, dozens of Afghan clerics had appealed to Samiul to use his influence with Afghanistan's Taliban to plot a path to peace that would end the 17-year-long war there.
Pakistan's President Arif Alvi and Prime Minister Imran Khan condemned Haq's killing.
"We lost a great scholar and religious leader today," said Khan in a statement from China where he is on an official visit.
Khan was widely criticized for embracing Samiul ahead of Pakistan's July elections that put the former cricketer-turned-politician in power. Khan's provincial government in Khyber Pakhtunkhwa donated millions of dollars to Haq's hard-line seminary. He defended the move saying he wanted to see Pakistan's thousands of madrassas, or religious schools, broaden their curriculum.
Samiul's funeral is expected to be held Saturday in Akora Khattak.