Agha Aftab Haider Jaffri, a leader of the Jaffaria Alliance Pakistan, and Mirza Shahid Ali were killed in Saddar area of Karachi.
Police officials said gunmen riding a motorcycle opened fire at Jaffri's car and killed both men instantly.
Members of the Shia community organised a protest after learning about the killing of Jaffri.
In a separate development, the bomb disposal squad defused a bomb containing five kilograms of explosives that was planted at a gate of the Mazar-e-Quaid, the mausoleum of Mohammad Ali Jinnah, the founder of Pakistan.
Witnesses said some men travelling in a car had planted the bomb at the gate of the mausoleum.
