Motorists are being warned of delays and diversions after an accident on Slack Hill.
Police said they received a call at 11.55am about a collision involving two cars.
Derbyshire Fire and Rescue Service said one of the vehicles was on its side. Three people had to be rescued by the fire service.
One person was taken to hospital in Sheffield by air ambulance and two other people were taken to hospital in Derby by ambulance.
The A632 Slack Hill has been closed, with traffic being diverted by the Kelstedge Inn. The road is expected to remain closed for some time and motorists are being advised to use an alternative route.