The 53-year-old driver of a Mercedes car died at the scene of the crash on the A78, near Hunterston Roundabout, at about 10:10 on Saturday.
The 60-year-old male driver of the bus and a 69-year-old female passenger suffered head injuries.
A further 57-year-old male passenger was said to be serious but stable.
The other seven bus passengers have left hospital after treatment.
Police said the name of the car driver would not be released.
Sgt Iain Pittams said: "Enquiries into the incident are continuing and we are asking that anyone who saw the crash or who has any information about it to contact police."
The driver of a bus and two passengers injured in a collision with a car in Ayrshire remain in a serious condition in hospital, police have said.