Groundwater depletion is a problem in many parts the world. We developed an approach to investigate the drivers of groundwater depletion in data-scarce regions. The approach combines natural and human-induced drivers, with the latter focusing on the link between human activities and government policies. We tested the approach in Wadi Zabid, Yemen. Forty years of rainfall-runoff data were analyzed, alongside changes in land cover, groundwater abstraction and related policies. No decrease in rainfall was observed, but runoff did decrease slightly. Significant expansion of agricultural lands led to increased demand for irrigation water, which was provided by drilling wells and building water harvesting/diversion structures. In Wadi Zabid, human activities, stimulated by policy measures, were the main drivers of groundwater depletion (water table here fell by 1 m/yr on average over 1972–2016). We conclude that combining natural and human-induced factors is indeed a valuable approach for investigating groundwater depletion drivers.