The man and woman in the Vauxhall Corsa died at the scene of the crash, which was on the A60 Mansfield Road in Nottinghamshire.
The bus driver and three passengers were taken to hospital.
The bus and car collided at about 21:45 GMT on Wednesday, between the junctions with Forest Lane and Kighill Lane, near Ravenshead.
Nottinghamshire Police has asked for witnesses or anyone with information to contact them.
Two people have died and four people have been injured after a car and a bus collided.