The long-term trends and seasonal patterns of stream water chemical composition in a small remote forested karst catchment, were investigated from 1978 to 2018. Calcium, magnesium, and bicarbonates, the dominant ions, increased over the period together with temperature, while sulfates decreased. Carbonate and sulfate mineral dissolution was the main source of these elements. These trends and the seasonal opposite patterns of discharge vs. temperature, calcite saturation index vs. pCO2 and bicarbonate vs. sulfates, suggested the influence of discharge, of reduced long-range atmospheric pollution, and of increasing air temperature on biological activity and carbonate dissolution. Furthermore, the hydrological regime controlled the seasonal stream water chemical composition and fluxes by: (i) a dilution during the high discharge period, (ii) a change in the contribution rate of the waters draining different lithological areas in the catchment, e.g., the increased sulfates to bicarbonates ratio during summer low flows, with a maximum alkalinity decrease of 24%, and (iii) a "piston" and a "flushing" effects of dissolved elements stored in soils and epikarst with the first autumn heavy rains. Long-term stream water hydrochemical surveys of karst system have proved to be powerful indicators of biogeochemical processes, water sources and pathways under variable natural and anthropogenic environmental pressure conditions.