Structural landform evolution and hydrogeochemical analyses are crucial for understanding the characteristics of karst groundwater systems and the development of deep karst formed by complex aquifers in a tectonic collision zone. Detailed structural landform evolution analysis was carried out along the large‐scale anticlinorium to investigate the temporal evolution of karst aquifer systems and karstification. Results showed that the tectonic activity included weak horizontal compression and slow vertical uplift during the Triassic to Middle Jurassic, forming a denuded clastic platform. This period was mainly preserved in the geological record as burial karst. From the Late Jurassic to the Early Cretaceous, the study area was strongly compressed by S–N‐trending stress, and developed E–W‐trending high‐angle imbricate thrust structures, which controlled the formation of folded and fault‐blocked mountains. Vertical multilayered strata underwent a strong horizontal extrusion, forming a large‐scale anticlinorium with secondary folds and faults. With the exposure of carbonate rocks due to rapid crustal uplift, karst began to develop, forming a vertical multilayer karst aquifer system and controlling the distribution of karst groundwater. The Fangxian faulted basin was formed from the Late Cretaceous to the Paleogene, whereby landforms were dominated by intermountain basins. Slow crustal uplift caused the retreat of the denudation line to the east, leading to an increase in hydrodynamic conditions and karstification, and the initiation of early karst groundwater systems. Since the Neogene, intermittent and rapid crustal uplift has led to the deepening of rivers, resulting in the formation of peak clusters and canyons, the development of deep karst, and the complete formation of karst groundwater systems. Combined with hydrogeochemical and borehole data, local, intermediate, and regional karst groundwater systems were identified. It has vital significance to the geological route selection or construction of deep‐buried tunnels and the utilization of karst groundwater.