Muttahida Qaumi Movement legislator Manzar Imam and his guard were gunned down in Orangi Town area of Karachi.
Another bodyguard was injured in the shooting, police officials said.
No group claimed responsibility for the attack.
Karachi has for long witnesses bloody clashes between workers of various political parties.
Reports said Imam's killing triggered tension in several areas of Karachi that are controlled by the MQM, which is a member of the Pakistan People's Party-led governments at the Centre and in southern Sindh province.