A Pakistan International Airlines Airbus A320 flying from Lahore has crashed in the densely populated Model Colony residential area of Karachi.
Flight PK8303, carrying 91 passengers and eight crew, crashed on approach to the busy Jinnah International Airport.
The provincial health minister said at least 11 people had died, but a far higher toll is feared. At least two passengers are confirmed survivors.
The pilot had reported loss of engines and then issued a Mayday.
TV footage showed rescue crews combing through debris strewn across the streets of Model Colony, 3.2km (two miles) north-east of the airport. A number of houses have been destroyed.
The plane had lost contact with air traffic control just after 14:30 local time (09:30 GMT), an airline spokesman said.