The president of the Ittehad Ulema Afghanistan - Maulana Sheikh Abdullah Zakiri, 84 - was gunned down in provincial capital Quetta yesterday.
He was playing an important role in initiating talks between the Taliban and Karzai's government, Dawn daily quoted its sources as saying today.
Men on a motorcycle fired at Zakiri's car on Sabzal Road, police said. He was hit by a bullet in his chest.
"Sheikh Zakiri was a prominent religious leader of Afghanistan and chief of an organisation of ulema from the country," Balochistan Home Secretary Syed Asadur Rehman Gilani said.
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The attackers escaped but police raided several places to trace them after getting information about them.
Zakiri had close relations with the Taliban and had fought against Soviet forces in Afghanistan. Reports said the Afghan Taliban confirmed the incident and blamed "enemies of the religion and Afghanistan" for the murder.
The Afghan government has denied any involvement in such killings in Pakistan and linked the incidents to internal differences of the Taliban.
Two top Taliban leaders, Mullah Noorullah Hotak and Mullah Abdul Malik, were killed in Quetta in December.
The Afghan Taliban have claimed that over 10 of their leaders have been killed in Quetta by unknown people during the past two years.
Some of the dead leaders were making efforts for reconciliation between the Taliban and the Afghan government.