Khalid Mehmood Soomro, senior leader of the Jamiat Ulema-i-Islam Fazl (JUI-F), was leaving a mosque in Sukkur after morning prayers when he was targeted by unknown gunmen.
JUI-F chief Maulana Fazlur Rehman told media that Soomro was the victim of a terrorist attack.
"The government should order immediate action to arrest the attackers," Fazl said.
Soomro hailed from Larkana district of Sindh and was also the secretary general of the Sindh branch of the party.
He was a key leader and also elected as a senator from his party and served in the parliament from 2006-2012.
Prime Minister Nawaz Sharif condemned the killing and asked the provincial government to arrest the culprits.