Significant losses from drought events of the 1990s and the early twenty first century indicate the growing vulnerability of the U.S. agricultural production to drought. Vulnerability of the High Plains agriculture to recurring drought events reflects a complex interplay of several major factors that influence land use in the region: climatic processes, surface and ground water availability, cost of irrigation, political and demographic trends, and agricultural decision-making play a crucial role in constructing of overall vulnerability. Some portions of the High Plains region with limited water resources, including Texas Panhandle, are particularly vulnerable to recurring droughts: ground water, withdrawn from the depleting High Plains aquifer, is the principle source of water for the area. This paper discusses vulnerability of several major land use types within the High Plains to recurring drought and depleting water resources. Case studies developed in this study focus on the examples of land use types of Nebraska and Texas, including rangelands and croplands. Characteristics of land use types, factors underlying their vulnerability and methods of spatial analysis of drought vulnerability are discussed.