The crash happened on Meaver Road in Mullion, on the Lizard Peninsula
A young boy and a woman in her 30s have sustained "life-threatening injuries" in a crash involving a double-decker school bus.
The crash happened on Meaver Road in Mullion, on the Lizard Peninsula, at about 08:40 BST on Monday.
Devon and Cornwall Police confirmed the child and the woman, who were in a Vauxhall Astra, sustained "life-threatening injuries" and were being treated in hospital.
Four children on the bus were treated for minor injuries.
One of the seriously-injured casualties was airlifted to Plymouth and the other was taken by land to Royal Cornwall Hospital near Truro, officers said.
HM Coastguard said two of its rescue helicopters from St Athan and Newquay attended, and coastguard rescue teams from Falmouth, Mullion and Porthoustock were also called.
South Western Ambulance Service and Cornwall Fire and Rescue Service also attended.
Mullion Community Fire Station said the crash happened between Mullion School and the Parkdean Resorts Lizard Point Holiday Park.
Sgt Phil Brown, of the Devon and Cornwall Police serious collision team, said: "We owe the people involved in this collision a full and frank investigation to find out the circumstances."
Insp Tony Hannaford said incidents with children were "distressing incidents to deal with"
Insp Tony Hannaford, from the roads policing team, described the crash as "complex" and said the force had called in forensic collision investigators and a drone team to provide aerial footage of the scene.
He said incidents involving children were often "more challenging and distressing to deal with" and officers were in contact with the school to ensure those involved were "looked after".
The Truro and Penwith Academy Trust confirmed the bus involved had been carrying students from Mullion School.
It added: "We can confirm some students had relatively minor injuries that were treated quickly by first responders. The initial response was exceptionally well-supported by the emergency services, and our students are receiving ongoing support from school staff who moved to assist with the scene."
The road is expected to remain closed into the evening. Any witnesses to the crash are urged to contact police.
A spokesperson for Cornwall Council said: "Our thoughts are with all of those affected by this morning’s incident and our education and school transport teams are doing all they can to support the pupils and staff at the school."
