It happened at about 5.45pm half way up Rectory Hill in the Castel and all three emergency services were called to the scene.
The road was completely blocked to traffic from the bottom of the hill to the top.
Civil Protection officers were also called to assist with diverting traffic away from the area.
At 9.45pm Inspector Tom Marshall told the Guernsey Press: 'As a result of the collision, the motorcycle rider has sadly died.
'We are not releasing details of the rider at this time because we need to speak to the family.'
Anyone who witnessed the collision, or has any information regarding it, is asked to get in contact with the police on 222 222.
By the time Inspector Marshall got to the scene there were no passengers on the bus, and no other injuries were reported.
The bus was towed away at 10pm and some other nearby vehicles were recovered as part of the investigation.
A more detailed media release is expected tomorrow [Tuesday].