The vehicle blew up outside a KFC fast-food outlet at about 8.40am (0340 GMT) on Tuesday, gutting the restaurant and shattering the windows of a nearby six-storey office block housing oil and gas exploration firms.
Earlier reports put the toll at six killed.
About 15 other people were wounded, some critically, police and doctors said.
Provincial authorities said they suspected Muslim fighters and cast doubt on a claim of responsibility by a separatist group from nearby Baluchistan province which said it had targeted an office of a state-run Pakistani oil company.
Manzoor Mughal, chief of investigation for Karachi police, said two of the dead were security guards for the Muslim Commercial Bank.
"This is an act of terrorism and apparently the KFC was the
target," added Mughal. "Our initial findings were that an explosive was placed inside a car."
Hundreds of people gathered at the site of the blast, near the Pearl Intercontinental Hotel that is popular with foreign tourists and business people.
There are other five-star hotels in the area, as well.
The bomb caused casualties
in an office block
England's touring cricket team is due to stay there next month.
No one had claimed responsibility for the attack, Information Minister Shaikh Rashid Ahmed told Reuters.
The bomb struck as commuters were heading to offices and shops in the crowded business hub. The restaurant was closed at the time.
Some banks on the ground floor of the office building
felt the force of the blast, which blew other cars on the road
to pieces. Tenants of the building include Pakistan Petroleum
Another KFC restaurant and a McDonald's outlet came under
attack in September in Karachi.