Freshwater scarcity is a major issue in Rayalaseema region in Andhra Pradesh (India). Groundwater is the primary source of drinking and irrigation water in Anantapur district, Andhra Pradesh, India. Therefore, it is important to identify areas having groundwater potential; however, the current methods of groundwater exploration consume a lot of time and money. Analytic Hierarchy Process (AHP)-based spatial model is used to identify groundwater potential zones in Anantapur using remote sensing and GIS-based decision support system. Thematic layers considered in this study were geology, geomorphology, soils, land use land cover (LULC), lineament density (LD), drainage density (DD), slope, and rainfall. According to Saaty’s AHP, all these themes and individual features were weighted according to their relative importance in groundwater occurrence. Thematic layers were finally combined using ArcGIS to prepare a groundwater potential zone map. The high weighted value area was considered a groundwater prospecting region. Accordingly, the GWPZ map was classified into four categories: very good, good, moderate, and poor. The very good GWPZ area is 77.37 km2 (24.93%) of the total study area. The northeastern and southeastern sections of the study area, as well as some medium patches in the center and western regions, are covered by moderate GWPZs, which cover an area of 53.07 km2 (17.10%). However, the GWP in the study area’s central, southwestern, and northern portions is poor, encompassing an area of approximately 79.31 km2 (25.56%). Finally, RS and GIS techniques are highly effective and useful for identifying GWPZs.