Groundwater prospective mapping has several functions, including irrigation water supply, domestic and industrial water uses. This study aimed to map prospective groundwater zones in the Meki watershed, Ethiopia. Climate, physiographic, geologic, and satellite image data were used as factors for groundwater mapping. Thematic maps of rainfall, land use/land cover, soil, drainage density, slope, geomorphology, elevation, and geology were analyzed using ArcGIS 10.4. Land use/land cover classification was based on the 2016 satellite images. The PCI Geomatica 10.3 package was used to produce the lineament map, and eventually, the lineament density map was produced using ArcGIS 10.4. We used the Analytical Hierarchical Process (AHP) tool to prioritize the different factors affecting the groundwater condition of the area. The reclassified thematic layers of the factors were overlaid using weighted linear combination analysis in Arc GIS 10.4. The result depicted that geomorphology, geology, and land slope shared a higher weight having 26%, 20%, and 18%, respectively. Small areal coverage is accounted for by very high and low zones of groundwater potential, and a significant portion of the watershed falls in high (30% of the watershed) to moderate (35% of the watershed) groundwater potential zones indicating good groundwater prospects in the region. The produced groundwater potential map was validated using data from groundwater well inventories. According to the groundwater flow vector, groundwater flows primarily from the northwest to the southeast. Therefore, this study's results could help locate potential groundwater well sites for various purposes in the Meki watershed, Ethiopia.