Shaukat Sherazi, 45, and another person were gunned down by unknown bike-borne assailants in the Old City area.
Police said the murder appeared to be sectarian.
"They were sitting in their office at Mithadar when the gunmen came on motorcycles and fired upon them," senior police official Sheraz Nasir said.
Sherazi was also a member of the south wing of Jaffaria Alliance Pakistan.
The incident has fuelled tension in the Shia-dominated areas of Karachi. Majlis-e-Wahdatul Muslimeen (MWM) has announced it would hold a nationwide protest on Friday against the killing of Sherazi.
Karachi, with a population of 18 million that contributes 42 per cent to the country's GDP, is rife for years by ethnic, sectarian and political violence.
In other incidents of targeted killings four people were murdered in the city.
A 40 year-old owner of a marble factory was shot dead by unidentified armed men for his refusal to pay extortion money.
Another person was shot dead in Liaquatabad while a woman was gunned down in Keamari.
