Police called out to investigate reports of a car travelling on the wrong side of the M1 reached the scene to discover two cars had collided head-on.
Four people were taken to hospital after the crash on the Pacific Motorway near Mooney Mooney about 8.30pm on Wednesday night, which closed all northbound lanes.
Drivers are facing significant delays.
A man who was driving a silver Ford Falcon has been taken to Gosford Hospital in a critical condition.
A woman travelling in the other vehicle was flown to Royal North Shore Hospital with two broken legs. A man and woman who were in car with her were taken by road ambulance to Royal North Shore.
Police said at 10pm that all northbound lanes were expected to remain closed for hours.
Traffic is being diverted onto the Old Pacific Highway at the Hawkesbury River Bridge. Drivers can rejoin the M1 Pacific Motorway at Mount White.
B-Double drivers are advised to avoid the area or delay their journey as the diversion is not a suitable route for them.
Southbound traffic is not affected.
Anyone with information is asked to contact Crime Stoppers on 1800 333 000.