The collision between a white Volkswagen Polo and a Scania double-decker bus happened at about 9.20pm between Wisbech and Guyhirn.
The driver of the car, an 18-year old woman from Littleport was pronounced dead at the scene.
Two passengers from the car, an 18-year-old woman and a 25-year-old man, were taken to Queen Elizabeth Hospital, in King’s Lynn, with serious injuries.
No one on the bus, including the driver, a 37-year-old woman, required hospital treatment. It is not clear how many passengers were on the bus but there were at least four.
An investigation is ongoing and no arrests have been made.
The road was not re-opened until about 5.30pm.
Anyone who witnessed the crash or who has dashcam footage of the moments leading up to it should contact police via the web chat function https://bit.ly/3vsiYDw, online forms www.cambs.police.uk/report or by calling 101, quoting incident 523 of 19 May.
Officers are also appealing for anyone who was a passenger on the bus and did not provide their details at the scene, to please get in touch via the above methods.