Following the two-vehicle collision, at Blue Bank on the A169 near Sleights, both drivers were described as "walking wounded" and both vehicles were on fire, according to police.
At least one driver was taken to James Cook University Hospital, Middlesbrough, but the extent of their injuries is not known.
North Yorkshire Police, North Yorkshire Fire and Rescue Service, Yorkshire Air Ambulance and the ambulance service attended the incident at around 8pm.
Road closures were put in place at the two Goathland turn offs and a cordon was put in place to allow emergency services to deal with the incident.
Both cars were completely burned out by the fire and fire crews extinguished the vehicles.
The road is believed to have been reopened on Sunday morning at around 9am.