Police officials said it appeared that six to eight assailants on motorbikes 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 area of Karachi.
"It was a targeted attack," Sindh Police Inspector General Ghulam Haider Jamali told reporters.
The attackers killed 47 people and wounded more than 20 others before fleeing from the scene.
A senior police official said the attackers entered the bus and shot the passengers in the head.
Nobody took the responsibility but the Taliban and groups like Lashkar-e-Jhangvi often carry out such attack.
However, a pamphlet of terrorist group Islamic State was recovered from the scene, according to a police official but government has not so far named any group for the attack.
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