The bomb, hidden in a motorcycle, was detonated by remote control as the bus was passing through Mastung district, 50 km south of the provincial capital of Quetta.
Officials confirmed the death of two people.
State-run television reported that nearly 50 people, including women and children, were injured.
The condition of seven of the injured was critical, doctors at a local hospital said.
The injured were taken to a nearby hospital and those in a critical condition were later shifted to Quetta.
Police said that the intended target of the bombing might have been a bus with Shia pilgrims that passed the area minutes before the explosion.
No group claimed responsibility for the attack.
Balochistan has witnessed a string of sectarian attacks that targeted the minority Shia community.
Scores have died in these attacks.