The bomb was planted in a rickshaw which was parked near the mosque, police official Khaliq Sheikh said.
Ten kgs of explosives were used int he attack, IG Sindh, Iqbal Mahmood told reporters at the blast site.
"It was definitely targeted," he said.
The blast occurred soon after the Friday prayers in the Gizri area near the upscale Clifton locality.
This is the first time that such a major explosion has taken place in the Gizri area, close to Clifton.
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Television footage showed that the blast caused massive damage with the wall of a nearby house completely destroyed and windows of nearby buildings shattered.
Geo channel reported that at least 10 vehicles, six rickshaws and many motorcycles were completely destroyed or damaged in the blast.
No group claimed responsibility for the attack though such incidents are usually blamed on the banned Pakistani Taliban.
The attack came a day after a senior Pakistani police officer, who had survived several attacks for his anti-militant campaigns, and three others were killed in a Taliban suicide bombing in Pakistan's largest city.