Hume Police District senior constable Adam Churchill said a silver Toyota Corolla was travelling at the rear of a maroon Hyundai i30 when it collided with the back of the car.
It is believed both cars careered from the Hume Highway down an embankment in the median strip.
Both cars crashed into trees and sustained significant damage/
The driver of the Toyota Corolla is a 38-year-old man with a female passenger in her late 20s.
The woman will be airlifted to hospital by the TOLL Rescue Helicopter service.
The man was taken to Goulburn Base Hospital by road ambulance.
A 24-year-old man in the Hyundai i30 suffered a broken foot and ankle.
NSW Police Rescue was required to cut open the door of the Toyota Corolla.
Motorists are advised to allow extra travel time as traffic remains heavy in the area.
Traffic remains heavy on the Hume Highway at Marulan after a two-vehicle crash.
A Transport Management Centre spokeswoman said one of two northbound lanes was closed for emergency services.
The crash has also affected southbound traffic on the highway.
A helicopter is currently en-route to the nearby heavy vehicle safety station.
The Crash Investigation Unit, emergency services, Transport for NSW and Rural Fire Service crews are at the scene.
Motorists are advised to expect significant delays and exercise caution.
A two-car crash has caused traffic delays on the Hume Highway at Marulan.
At about midday on Monday, October 7, the RFS were notified of the accident near Highland Way.
NSW RFS Southern Tablelands Zone operational officer Lachlan Gilchrist said crews were on top of things.
"Crews from the Marulan Rural Fire Brigade are on scene at the moment," officer Gilchrist said.
"They are focusing on providing fire protection."
Paramedics are also at the scene treating the patients. The Hume Highway remains open.