The A19 is closed in both directions between A61 at Thirsk and A168 at North Kilvington after the collision at around 10.50am this morning (Saturday).
North Yorkshire Police and North Yorkshire Fire and Rescue Service were called to the scene.
The fire service said crews freed an elderly man from a vehicle after the crash.
Highways England said it has also received reports of a fire on the stretch of road.
Diversions are now in place but motorists have been told to expect delays.