Twelve passengers died at the scene and another died later at a hospital, the governor of Imbabura province Paolina Vercoutere told reporters.
The accident happened around 8:00 pm Sunday (0100 GMT) near the town of Otavalo when the bus hurtled off the road and overturned, emergency services said.
In July, 14 people were killed and 30 injured in another bus accident in the center of the country.
Deadly road accidents are common in Ecuador. A local non-governmental organization estimates that at least 13 people are killed and 142 injured in road accidents every day, the vast majority as a result of human error.