Mufti Abdul Majeed Deenpuri, 60, a well known religious scholar and head at Jamia Binoria Uloom Islamia was shot dead with two other colleagues on the busy Shahrah-e-Faisal road near nursery in the afternoon.
Armed men sprayed bullets on the pick up van in which Mufti Deenpuri was going as it slowed down near a traffic signal.
The news of the death of the Mufti and his colleagues spread in the city and students, followers and supporters of the Jamia Binoria school of thought protested in several areas with several people injured in some areas due to the aerial firing.
Police and paramlitary rangers had to step in to control the situation and were present in large numbers when the funerals of the slain clerics was taken out near Numaish.
A senior police official said that pictures from close-circuit camera had shown a gunman rushing towards the van and opening fire on it.
He said Mufti Deenpuri and two other clerics and driver Hassaan Shah were also killed.
The police official didn't rule out the incident being a sectarian killing.
Police and rescue workers said that six other people had died in violence in other parts of the city most of them victims of target killings.
Two people were gunned down near the Northern Bypass area.
Earlier, three bodies, bearing torture marks, were found stuffed in gunny bags in Karachi's BaldiaTown area.
Police said the unfortunate men had been kidnapped a day earlier from Orangi.
