The shootout between the paramilitary rangers and militants took place in the Defence area of the city.
Three militants were killed and a senior official was injured, a spokesman of the Rangers said.
Those killed were said to be involved in terrorist attacks, kidnappings and extortion in the city, he said.
A huge cache of arms and ammunition was also recovered from the possession of the militants.
In a separate raid on the outskirts of Karachi, six militants of the Tehreek-e-Taliban Pakistan were arrested.