Epigenic karst systems exhibit strong connectivity to surface recharge. In land use dominated by extensive agriculture and farming, epigenic karst aquifers are highly vulnerable to surface contaminants from point and nonpoint sources. Currently, the karstic landscapes of the southeastern Kentucky platform (USA) are impacted by agriculture and the rapid proliferation of concentrated-animal-feeding operations. Analysis of karst aquifer responses to storm events provides qualitative information regarding aquifer–recharge flow paths and groundwater residence time, and knowledge of spatial and temporal variations in recharge and flow is crucial to the understanding of the fate of surface contaminants. Time-series correlation analyses on long-term physicochemical data recorded at the outlet of Grayson Gunnar Cave, an epigenic karst system located along the Cumberland escarpment in southeastern Kentucky, revealed the existence of two separate conduit branches responding 4–8 h apart from each other. Recorded storm response times range from 4 h for flushing and dilution to 7 h for recovery. An estimated 6 million L of stored groundwater is discharged from both branches during major storms, and the fastest responding branch accounts for the majority (80%) of the groundwater reserve being discharged through the spring. As evidenced by groundwater residence time (7 days), recharge is likely characterized by localized infiltration of rain water from subsurface sinkholes to the conduit branches with no contribution of regional or lateral groundwater flow.