Allama Ali Akbar Kumaili, the son of respected Shia scholar and Jafaria Alliance Pakistan chief Allama Abbas Kumaili, was targeted by unknown gunmen riding a motorbike near Bhangoria Goth in Azizabad, police said.
Ali Akbar was returning home with his children and guard from his ice factory, they said.
The guard also died after receiving bullet wounds.
A Mujlis-e-Wahdatul Muslimeen (MWM) spokesperson said Ali Akbar was shot near the factory and was rushed to a hospital where he succumbed to his bullet wounds.
MWM leader Allama Raja Nasir Abbas Jafri condemned the incident, saying target killings of Shia community was underway unhindered in Karachi and the government has failed to control it.
Jafaria Alliance has called for three days of mourning. This has been supported by the MWM.
President Mamnoon Hussain and Prime Minister Nawaz Sharif immediately condemned the killing.
Sharif said people would foil designs of terrorists through unity.
Prominent leaders and scholars of the Shia community have regularly been targetted in Karachi and other parts of Pakistan notably in Quetta in Balochistan.
Shias make up about 20 per cent of Sunni-majority Pakistan's population.
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