The Stagecoach bus and a Mercedes collided on the A78, near Hunterston roundabout at Fairlie, North Ayrshire, at about 10.10am yesterday.
The incident prompted a large response from the emergency services, who sent multiple vehicles, specialist teams and helicopters to the scene.
Police Scotland later confirmed that the 53-year-old man driving the Mercedes died at the scene. He was the only person in the car.
The male bus driver and a female passenger were taken by helicopter to Glasgow’s Queen Elizabeth University Hospital, where they were both treated for serious head injuries.
A further eight bus passengers – six women and two men – were taken by ambulance to Inverclyde Royal Hospital and Crosshouse Hospital for treatment.
The bus was travelling south and the silver Mercedes heading in the opposite direction when the crash happened.
A spokesman for the Scottish Ambulance Service said: “We received an emergency call shortly after 10am for a road traffic accident involving a bus.
“We responded with multiple vehicles, including six ambulances, one paramedic response unit, a full special operations response team, area services managers, the EMRS [Emergency Medical Retrieval Service] and two helicopters.
“This was a serious road traffic accident. We worked with our colleagues from Police Scotland and the fire service.”
The A78 was closed between the Hunterston roundabout and Clydeport roundabout to allow police to carry out investigations at the scene. Local diversions were in place.
A spokesman for Stagecoach West Scotland said: “We can confirm that a car was in collision with one of our vehicles operating the 585 service near Largs.
“Our first thoughts are with the people who have been involved in the incident.
“The safety of our passengers and staff is our highest priority and we are assisting the police fully.”
Police Scotland said a report will be sent to the procurator fiscal.
A spokeswoman said: “Inquiries into the crash are continuing. Anyone who witnessed it or has any information that will assist police with their inquiries is asked to contact the road policing department at Irvine police office via 101.”
The incident takes the death toll on Scotland’s roads to seven in just over a week.