The incident occurred within the campus of Sardar Bahadur Khan Women's University at Brewery Road.
Students and faculty members were in the stationary bus when a bomb planted inside went off.
They were waiting to go home after the end of classes.
Police officials said 11 girls, all students of the university, were killed.
Twenty-two injured people, most of them students, were taken to a nearby hospital.
Doctors described the condition of three of them as serious.
Several girls sustained severe burn injuries as the explosion triggered a fire in the bus.
Footage on television showed flames and black smoke emerging from the bus, which was reduced to a blackened heap of metal. Its roof was blown off and hung over the front.
Security forces cordoned off the area and launched a search operation.
The blast caused panic in the area and the university was evacuated.
No group claimed responsibility for the attack.
The blast occurred hours after militants attacked and destroyed a historic 121-year-old building in Ziarat, about 120 km from Quetta, that was used by Pakistan's founder Muhammad Ali Jinnah in the last days of his life.
A policeman was killed in that attack, which was claimed by the Balochistan Liberation Army.