Firefighters and rescue workers rushed to the Gul Plaza shortly after 10pm local time on Saturday following reports of the blaze, police and rescuer officials said.
According to local media, most shop owners were closing their stores or had already left when the fire broke out and spread quickly.
The cause of the fire was not immediately known. Police said an investigation would be launched once the blaze was extinguished.
However, most structures in Karachi, and other parts of the country, lack fire prevention and firefighting systems, which often results in damages and casualties.
TV footage showed firefighters in protective gear battling the flames. Several fire trucks used ladders, water cannons and hoses to douse the building's floors, where flames shot out of windows and balconies.
Thick black smoke billowed into the night sky and was visible from several blocks away.
Authorities said the fire spread rapidly after erupting in an area where shopkeepers had stored imported garments, clothing and plastic household goods, which helped fuel the flames.
In November 2023, a fire tore through a shopping centre in Karachi, killing 10 people and injuring 22 others.
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