One person has been killed in a 2 car crash at Muswellbrook overnight.

Emergency services were called to Thomas Mitchell Drive at about 6.30pm on Wednesday to find a Hyundai Getz and a Nisaan Pulsar had collided, trapping three people.

The driver of the Hyundai, a 28-year-old man, died at the scene.

Police say the driver of the Nissan, a 20-year-old woman, was freed by Fire and Rescue NSW and airlifted to John Hunter Hospital in a serious condition. A 10-year-old girl, who was travelling in the back seat, was also flown to hospital suffering suspected fractures.

A seven-week-old boy in the same vehicle escaped injury but was taken to hospital to be checked as a precaution.

Officers from Hunter Valley Police District established a crime scene which is being forensically examined and have commenced an investigation into the circumstances surrounding the crash.

A report will be prepared for the Coroner.