It happened around 7 a.m. at the intersection of Bridge and Tacony streets just off I-95.
Police say the motorcycle collided with a sedan, and the 41-year-old motorcyclist was ejected from the bike.
He was pronounced dead at the scene. His name has not been released.
Police say the driver of the Toyota was hospitalized but there is no update on that person's condition.
The cause of the crash remains under investigation.