Detailed geomorphological analysis has revealed that subhorizontal gypsum caves in the Northern Apennines (Italy) cut across bedding planes. These cave levels formed during cold periods with stable river beds, and are coeval with fluvial terraces of rivers that flow perpendicular to the strike of bedding in gypsum monoclines. When rivers entrench, renewed cave formation occurs very rapidly, resulting in the formation of a lower level. River aggradation causes cave alluviation and upward dissolution (paragenesis) in passages nearest to the river beds. The U-Th dating of calcite speleothems provides a minimum age for the formation of the cave passage in which they grew, which in turn provides age control on cave levels. The ages of all speleothems coincide with warmer and wetter periods when CO2 availability in the soils covering these gypsum areas was greater. This climate-driven speleogenetic model of epigenic gypsum caves in moderately to rapidly uplifting areas in temperate regions might be generally applicable to karst systems in different geological and climatic conditions.