Fire crews from Worksop, Edwinstowe and a specialist rescue unit from Tuxford were called out at 1.10pm.
They found two cars, a red Renault Scenic and a silver Hyundai, had collided head-on on the 60mph road.
Three adults and a girl were trapped inside the Renault and were cut free by fire fighters.
The male driver was air lifted to hospital with serious, but not life threatening, injuries.
A rear passenger was also hurt and taken to hospital, while the young girl and a front female passenger escaped with only minor injuries.
In the other car, the male driver was trapped. He was cut out by fire fighters and taken to hospital with chest pains and a leg injury.
A boy was already out of the car when emergency services arrived. He was taken for a check-up.
The last fire crews left the scene at 3.45pm. The road was closed for around three hours while police investigated the cause of the crash.