The violence came even as Pakistanis celebrated Allama Iqbal day today.
Police said gunmen shot dead six people in Mauripur, Shersha, Gulzar Hijri, Rehri Goath and Korangi areas of Karachi.
Meanwhile, activists of little known Pasban-e-Aza party clashed with police after being denied a path to the Governor's house to march to present a resolution.
They were protesting the targeting of Shia Muslims in violence in Karachi.
Several activists were hurt when the police stopped the rally and refused to let them proceed. Police said the Governor's House was in the red zone where protests are not allowed.
The police then resorted to aerial firing and tear gas shelling after protesters refused the yield. The protesters in turn set tires on fire and also torched a bus.
A number of Shia Muslims have become victims of recent killings. Earlier this week, prominent Shia leader Allama Aftab Ahmed Jaffery - the deputy secretary general of Majlis-e-Wahdat-e-Muslimeen (MWM) -- as well as the chief of the Palestine Foundation, were shot dead.