DSP Mumtaz Ali Shah was badly wounded when two unknown gunmen opened fire on his car in Model Colony near Malir Check Post while he was on way to work.
Shah was rushed to hospital but he succumbed to his injuries en route.
Police said that DSP Shah was deployed at Landhi jail.
The incident comes at a time when Pakistan's paramilitary forces have launched a crackdown to restore the alarming law and order situation in Karachi, Pakistan's largest city and commercial hub.