Ambulance NSW responded to a two-vehicle accident just south of Molong at about 3.15pm on Thursday.
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Four people were injured in the crash between a car and a truck.
A woman, approximately 40 years of age, is in a critical condition after being transported to Westmead Hospital by helicopter with a serious head injury.
A boy sustained a fractured femur and suspected abdominal and pelvic injuries and was transported by a second helicopter to Westmead Children’s Hospital in a serious condition.
Two other patients – an elderly woman and a young girl – have been transported to Orange hospital by road with minor injuries.
Seven paramedic crews and two air ambulances attended the scene.
Police diverted traffic from the Mitchell Highway through Peabody Road, The Escort Way and Amaroo Road, while heavy vehicles used The Escort Way and the Northern Distributor Road.
Fire and Rescue NSW was also at the scene.
The Crash Investigations Unit is investigating the incident.