Karst areas and their catchments pose a great challenge for protection because fast conduit flow results in low natural attenuation of anthropogenic contaminants. Studies of the hydrochemistry of karst sources and river solutes are an important tool for securing and managing water resources. A study of the geochemical downriver evolution of the Wiesent River and its tributaries, located in a typical karst terrain, revealed unexpected downstream decreases of nitrate with maximum mean values of 30 mg/L at the source to minimum values of 18 mg/L near the river mouth. This trend persisted over the length of the river even though increased agricultural activities are evident in the downstream section of the catchment. This pattern is caused by fertilizer inputs via diffusive and fast conduits flow from karst lithology in the upstream area that may have reached the river's source even from beyond the hydrological catchment boundaries. Further downstream, these influences became diluted by tributary inputs that drain subcatchments dominated by claystone and sandstone lithologies that increased potassium and sulphate concentrations. Our findings indicate that bedrock geology remains the dominant control on the major ion chemistry of the Wiesent River and that agricultural influences are strongest near the headwaters despite increased land use further downstream, due to long‐term storage and accumulation in karst aquifers. This feature may not be unique to the Wiesent River system, as carbonates cover significant portions of the Earth's surface and subsequent work in other river systems could establish whether such patterns are ubiquitous worldwide.