One MQM worker was injured in the attack on an office of the party, police officials said.
Four armed men, who were riding on motorcycles, opened fire at the MQM office while a group of workers was celebrating the party's founding day.
Two MQM workers were killed instantly and two more injured. One of the wounded men succumbed to his injuries in hospital.
A large number of MQM leaders and workers gathered at the hospital and protested against the attack.
Large police and paramilitary contingents were deployed in the area of the attack with armoured personnel carriers.
No one claimed responsibility for the killings.