The High Oum-Er-Rbia basin, located in the Moroccan Middle Atlas, is a karstic region with significant water sources that have essential functions regarding agriculture, hydropower production, industrial and drinking water. The region contains abundant wetlands, especially springs, rivers and natural lakes. These systems are highly sensitive to the effects of climate change, experiencing considerable lake level, water chemistry, and biological fluctuations in response to regional hydrological balances. This study focuses on the hydrogeochemical processes and mechanisms that control the chemical composition and variability of Azigza Lake, a typical tectono-karstic lake system of the region. Water monitoring was implemented from July 2013 to October 2014 with a monthly water sampling for physicochemical measurements and major ion concentration analyses of lake water and the surrounding groundwater. Both waters show a relatively low salinity due to the fresh input from the Lower Jurassic karst formation. Lake waters are slightly alkaline and of the calcium-magnesium-bicarbonate type. The geochemistry of the lake waters is mainly controlled by carbonate weathering through water–rock interaction and, to a lesser extent, by cation exchange and precipitation of carbonate minerals. The hydrochemistry of the lake showed clear responses to seasonal changes in precipitation and evaporation, with higher conductivity during the wet period. During the beginning of the wet season, groundwater evolution could be explained by a simple first flush stormwater. The rapid response of lake water to subsurface and underground waters confirms the dominance of an underground conduct flow regime. These changes and behaviors highlight the sensitivity of Azigza system to regional hydrological and climatic changes.