According to the Coatesville Area School District, a driver was transporting high school students near the 300 block of Charles Street when a bullet went through the windshield.
The shooting happened sometime before 3 p.m.
No one on the bus was hit and no injuries were reported.
"Students on the bus are safe, as is the driver, and police are on the scene. We are extremely grateful for the calm reaction of our driver and the support of police," the school district said in a statement.
Further details on the shooting have not been released.
"No child should be subjected to gunfire on a school bus. This is an active, high-priority investigation," the Chester County District Attorney's office said in a statement.
As a result of the shooting, Thursday night's football game against Downingtown East High School has been canceled.
Anyone with information on the shooting is asked to call the Coatesville City Police Department at 610-384-2300.