Besides natural climate variability exacerbated by induced climate change, regulation of large surface water reservoirs and connected downstream irrigation systems have well-documented consequences on river discharge patterns. However, these natural and anthropogenic changes may also affect groundwater fluxes, which needs understanding for sustainable water resources planning and management. In the Nam Ngum River Basin, Laos, a major tributary of the Mekong River, hydropower dams were developed in the upper part of the basin, whilst the lower part is mostly undammed and intensively developed for agriculture and domestic water supply. This study investigates the changes to the river flow pattern and groundwater storage from the pristine period (pre-dam) to the near–present period (post-dam). Firstly, we analyzed observed discharge data to detect historical changes in river discharge in comparison with historical climate trend analyses. Secondly, we analyzed how natural and anthropogenic changes influenced groundwater storage in the sub-basin by looking at the incremental discharge between two gauging stations compared to total Equivalent Water Heights derived from the Gravity Recovery and Climate Experiment (GRACE). The results show that: (i) during the pristine conditions, the river discharge was highly seasonally dynamic. However, under post-dam conditions, there is diminished seasonal response with increased dry season flows and decreased monsoonal peak flows. This phenomenon showed a greater impact of human-made water infrastructures on river discharge than dependence on variability of climatic factors, as no trends in wet and dry season precipitation (Mann-Kendall test) are found in the times series; (ii) Incremental discharge increased by 38% compared to the pristine period, which is understood to be a result of higher groundwater discharge due to an increasing trend in total water storage as indicated by GRACE. Future research is underway to deconvolve the factors that are driving the changes in river and groundwater exchange. Â