Sajid Qureshi, in his early 50s, and his 26-year-old son Ovais were gunned down when they emerged from the mosque in North Nazimabad area after Friday prayers.
"Four armed men on motorcycles opened fire on the MPA and his son as they walked towards their car," Senior police official, Aamir Qureshi said.
Qureshi, a legislator of the Muttahida Quami Movement party (MQM), was killed instantly while his son succumbed to his injuries at a nearby hospital.
Qureshi was recently elected a member of the Sindh Assembly.
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No group claimed responsibility for the killings.
Soon after the incident tension spread in the city as the MQM also announced a three-day mourning period appealing for a complete strike on Saturday.
"We have been saying all along that our workers, members and lawmakers are being targeted by criminals given a free hand by the provincial government," senior MQM leader Rasheed Gondal told reporters.
Police said four people had been killed in incidents of firing and arson in some parts of the city, but situation was under control.
Protesters also set on fire vehicles in some areas as markets, shopping centres and petrol pumps started to close down.
Interior minister, Chaudhary Nisar Khan yesterday gave the provincial Sindh government one month to improve the law and order situation in Karachi or face action.
The MQM has been holding protests and peaceful strikes for the last one month over the killings and kidnappings of their workers and sympathisers in the city.
Incidents of targeted killings have increased dramatically in Karachi in the last two days with 14 people killed on Thursday and nine on Wednesday.