The A1 was shut in both directions between Stamford and Wittering following a crash involving two vehicles.
A Cambridgeshire police spokeswoman said the crash happened at 9.36am at the Carpenters Lodge junction.
The air ambulance landed at the scene, and fire and rescue, police and ambulance services are in attendance.
An East of England Ambulance Service spokesman said: “The East of England Ambulance Service NHS Trust (EEAST) received a call at 9.30am today to a report of a two vehicle road traffic collision on the A1 between Wittering and Stamford.
“Three ambulance crews, an ambulance officer and East Anglian Air Ambulance were dispatched.”
An elderly man was airlifted to Addenbrooke’s Hospital with serious leg injuries.
An elderly woman with back pain was taken to Addenbrooke’s Hospital.
A man with minor injuries was taken to Peterborough City Hospital for further treatment by land ambulance