It happened just before 7:15 a.m. near 17th Street and Lehigh Avenue.
According to police, the driver of the bus hit a trailer and then collided with two other vehicles.
The bus then went on to strike three homes before coming to a stop.
The bus driver and two attendants were injured. They were last reported to be hospitalized in stable condition.
Officials said no students were on the bus at the time.
The crash remains under investigation.