The 53-year-old man, who has not yet been named, died after the incident which happened on Doctors Bridge in Moss Delph Lane, Aughton, at 05:45 BST.
A Lancashire Police spokesman said: "Sadly [he] was pronounced dead at the scene, no-one else was injured and there were no passengers on the bus."
An investigation is under way to establish the cause of the crash, and witnesses are urged to contact police.
Sgt Adam Dawson, of the Roads Policing Unit, said: "Specialist officers are supporting the family at this difficult time and I would urge anyone with information who may have seen a black motorbike in the area prior to the incident to get in touch."
A man whose motorbike was in collision with a bus in Lancashire has died.