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Road accidents are common in Ethiopia, Africa’s second-most populous country, where road infrastructure is often inadequately maintained.
The bus, which was travelling from Dessie city in Amhara to the capital Addis Ababa, "plunged into a ravine approximately 100 metres deep (330 feet)", local authorities wrote on Facebook.
Twenty-eight people were killed and "many others have sustained minor or severe injuries", officials said, without giving exact figures.
The survivors were transported to medical facilities and an investigation is under way.
The total number of passengers has not been released.
Images shared by the official regional Facebook account showed a vehicle lying on a hillside, almost entirely obliterated.