Sutton Bank near Thirsk has been closed after a tanker came off the road on the steep hill, police said.
The A170 is shut between the top of the bank and the village of Sutton-under-Whitestonecliffe, North Yorkshire Police said.
The road is expected to be closed for several hours while the vehicle is recovered, the force added.
Drivers have been advised to avoid the area, with police thanking motorists for their understanding.