Police have said most of the missing are feared dead and rescue workers were trying to locate bodies in the debris.
The city's largest fire in over a decade started late on Saturday and quickly spread through the sprawling Gul Plaza shopping complex, famous for its 1,200 family-owned stores that sold wedding clothes, toys, crockery and much else.
Firefighters battled the flames that created an inferno inside the mall throughout the night and late into Sunday before bringing the blaze under control, although small fires continued to break out across the ruins.
Kosar Bano, a woman standing near the site, said six of her family had gone to the mall to shop for a wedding. The last time she heard from them, they said they would be home in 15 minutes.
"The only hope we have is how many hands we will find, how many fingers we will find, and how many legs we will find. That's it," she said.
Much of the once-imposing structure, larger than a football field, was reduced to a pile of ash and debris scattered across the street as rescue workers searched for a growing list of missing people.
Rizwan Ahmed from the Rescue 1122 group said on Tuesday that 21 people were killed in the blaze while another 63 were still missing, nearly three days after the fire began.
INVESTIGATION PROMISED
Relief workers dug through the rubble and brought out human remains in sacks before sending them for DNA testing.
Senior police official Syed Asad Raza told Reuters that 15 DNA samples had been collected by Monday night to help identify the bodies.
There was also rising anger at the scene with people blaming a delayed rescue effort and jeering the city's mayor when he showed up at the site nearly 24 hours after the fire began.
The government has said it will investigate the cause of the fire and the response.
Police also said that all but three of the mall's 16 exits were locked when the fire began around the mall's closing time.
Gul Plaza's management did not immediately respond to a request for comment from Reuters.
The blaze is Karachi's biggest since an industrial site went up in flames in 2012, killing more than 260 people. A court ruled in 2020 that the disaster involved arson.
(Reporting by Mohammed Waseem; Writing by Saad Sayeed; Editing by Raju Gopalakrishnan)
Grieving families and onlookers gather at the Gul Plaza fire site in Karachi, Pakistan, 19 January 2026. A deadly fire at Karachi?s Gul Plaza raged for over 24 hours, killing 21 people, including a firefighter, leaving many more missing, and destroying around 1,200 shops. Massive losses were reported as rescue efforts continued amid structural collapse risks. EPA/SHAHZAIB AKBER