The victims included an ambulance driver who responded to the clash, which caused a panic among residents in the Lyari Chakiwara area, Dawn News reported.
It was not clear who the combatants were or what triggered the shootout.
Four other people were injured in violent incidents around Karachi Friday, including two police officers who were the target of a large firecracker tossed at their station.
A sweep of a Karachi neighborhood Friday resulted in more than 300 suspects being detained. About 400 police officers and government Rangers took part in the door-to-door search of the provincial capital's Sohrab Goth area.
Dawn said the operation was ordered after a tip pointed them toward suspects involved in unspecified offenses.