About 9.45pm on Sunday, a bus was travelling east on Argyle Street when it mounted the footpath at the intersection of Church Street and struck three female pedestrians and a bus shelter.
Two of the women sustained minor injuries and have been taken to Westmead Hospital for treatment.
The 16-year-old girl was trapped under the bus until she was freed about 11.15pm.
She has been taken to Westmead Hospital in a critical condition.
The male bus driver was also taken to Westmead Hospital for treatment to shock. A blood sample will be obtained from the man at hospital.
It is believed the bus contained a small number of passengers at the time of the crash who were all uninjured.
A crime scene is in place at the location and officers from the Metropolitan Crash Investigation Unit have commenced inquiries.
Anyone with information about this incident is urged to contact Crime Stoppers: 1800 333 000 or https://nsw.crimestoppers.com.au.