The bus, operated by the Llamosas company, was heading from Chala, a town in Caraveli province, to Arequipa.
Both drivers reportedly survived the crash, which happened at kilometre 780 of the Pan-American Highway South.
Pictures from the scene of the crash show the wrecked bus at the bottom of a steep ravine – its windows completely shattered, bodywork badly damaged and roof caved in.
Waldor Llerena, Ocona’s district mayor, told radio station RPP that the terrain around the crash site is “very rugged”, and the area had a history of similar deadly accidents.