The Huaynaputina volcano, southern Peru, was the site of the largest historical eruption (VEI 6) in the Andes in 1600 CE, which occurred during the historic transition between the Inca Empire and the Viceroyalty of Peru. This event had severe consequences in the Central Andes and a global climatic impact. Spanish chronicles reported that at least 15 villages or settlements existed around the volcano, of which seven of them were totally destroyed by the eruption. Multidisciplinary studies have allowed us to identify and analyze the characteristics of six settlements buried by the eruption. Tephra fallout and pyroclastic current deposits (PDCs) had different impacts according to the settlement distance from the crater, the location with respect to the emplacement of PDCs along valleys, the geomorphological characteristics of the site, and type of constructions. Thus, Calicanto, Cojraque, and San Juan de Dios, located beneath the main axis of tephra dispersal lobe due west and/or on valley edges, were buried under several meters of pyroclastic deposits, while the villages of Estagagache, Chimpapampa, and Moro Moro, located to the S and SE of the lobe, were partially mantled by tephra. The 1600 CE Huaynaputina eruption created an important geological and cultural heritage, which has scientific, educational, and touristic values. Geo-touristic attractions are proposed based on identification, characterization, and qualitative evaluation of four groups totaling 17 geosites: volcanic geosites, volcanic-cultural geomorphosites, and hot springs. Seven geological roads along with seven viewpoints are proposed, which allow to value the most relevant landscapes, deposits and geological structures.