It is the Port's first road fatality for 2020.

The three other passengers of one of the vehicles involved in the collision along Tomago Road, two women aged 66 and 26 plus a 2 year old boy, suffered minor injuries.

Police said about 12.40pm on March 8 emergency services were called to Tomago Road after reports a Mitsubishi ASX had crashed into a tree after colliding with an Izuzu D-Max.

The collision is understood to have occurred in between the Masonite Road intersection and Old Punt Road. The road was closed in both directions until late on Sunday.

The Mitsubishi driver, a 75-year-old man, died at the scene.

The Izuzu driver, a 32-year-old man, sustained serious internal injuries and was airlifted to hospital by the Westpac Rescue Helicopter in a serious but stable condition.

The passengers of the Izuzu, the two women and 2-year-old boy, suffered minor injuries.

The Raymond Terrace-based Port Stehens SES Unit were among first responders to the scene.

"NSW SES rescue operators assisted NSW Ambulance intensive care paramedics with patient stabilisation. Hydraulic tools including spreaders were used on the vehicle to extricate the patient," an SES spokesperson said.

All patients were transferred to John Hunter Hospital for treatment.

Officers from Traffic and Highway Patrol Command established a crime scene, with the Crash Investigation Unit to investigate the circumstances surrounding the crash.

Any witnesses or anyone with dashcam vision who were in the area at the time are urged to come forward.

Contact Crime Stoppers on 1800 333 000 or nsw.crimestoppers.com.au.