This paper demonstrates the dominant hypogenic origin of caves and other karst features in the Prichernomorsky artesian basin, a major hydrogeological structure of the north Black Sea region. The basin occupies the south of the continental part of Ukraine and the north-central plain part of the Crimea Peninsula and is dominated by the Neogene (lower through middle Miocene) and Paleogene (Eocene through Paleocene) carbonate rocks, intercalated with sands, sandstones, clays and marls. The key study areas, in which some limestone members are exposed and partially drained, lie in the opposed sides of the basin: the north Black Sea region in the continental part (caves in Early Pliocene and Miocene limestones) and the Inner Range of the fore-mountain Crimea in the south, where the basin borders with the fold-trust Alpine mountain region (caves in Eocene and Paleocene limestones). The hypogenic origin of caves is strongly suggested by the analysis of cave morphology and occurrence relative to lithostratigraphy and structural features, cave sediments, isotopic and mineralogical data, and paleohydrogeological analysis. Despite of differences in age and diagenetic maturity of the host rocks, the caves demonstrate remarkable common features imposed by their common origin. The hypogenic speleogenetic model well explains observed specific hydrogeological and geochemical features of the regional multi-storey aquifer system in the central confined part of the basin. Hypogene speleogenesis is likely to play a role in the formation of carbonate-hosted reservoirs, as well as in the migration and accumulation of hydrocarbons in the Prichernomorsky basin.