Six to eight motorbike-borne assailants opened fire indiscriminately at the pink bus ferrying over 60 people to a Shia community centre to stop it, police said.
They first opened fire on the bus just near the Dow Medical College and then entered the bus when it stopped at Safoora Chorangi, Gulistan-e-Johar, a relatively deserted area on the outskirts of the city.
"It was a targeted attack," Sindh Police Inspector General Ghulam Haider Jamali told reporters.
The death toll could further rise as some persons are seriously injured. The injured and dead were shifted to various hospitals by rescue workers.
A senior police official said the attackers entered the bus and shot the passengers in the head.
A blood-stained pamphlet of terrorist group Islamic State was recovered from the scene, according to a police official. Balochistan-based militant group Jundullah, a splinter group of the Pakistani Taliban that has vowed allegiance to the ISIS, claimed responsibility for the attack.
However, government has not so far named any group for the attack.
The bus was disfigured with bullet holes and blood dripped out of its doors on to the concrete on the road.
A rescue official quoted a victim as saying that the attackers were dressed in police uniforms.
Jamali said initial investigations showed that the armed men used 9mm pistols in the massacre. Empty bullet shells of pistols and Kalashnikovs were found at the scene.
"This attack represents a senseless act of violence against a peaceful community. My thoughts and prayers are with the victims and the families of those killed and wounded in the attack," he said.
The Aga Khan noted that the Ismailis are a peaceful global community living in harmony with other religious and ethnic groups in many countries across the world, including in the Muslim world.
This was the worst attack targeting the members of the minority community after a suicide bomber in January blew himself up in a Shia mosque in Shikarpur in the Sindh province killing 61 worshippers and bystanders.
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