Rescue sources said unidentified attackers opened fire on the official vehicle of the Liaqatabad deputy superintendent of police in Azizabad locality of the city.
As a result, DSP Mohammad Hanif and his driver/gunman Sultan died on the spot.
Investigators said the attackers, said to be two in number and riding a motorcycle, fired at the police vehicle from the front.
Sources said they likely unloaded several magazines of a 9mm pistol as over a dozen shells were collected from the crime scene.
DIG West confirmed that two attackers riding a motorcycle carried out the attack.
Sindh Home Minister Sohail Anwar Siyal ordered an inquiry into the attack and directed for heightened security across the city.
Officials of the police are targeted in similar attacks in the metropolis.