Change in land use land-cover (LULC) is a paramount dynamic present-day challenging landscape process capable of altering the hydrological responses in the catchment. As the land use planners require updated and high-resolution land resources information, understanding land cover change-induced status due to anthropogenic activities is significant. In this study, multitemporal cloud-free satellite imageries for periods (1990, 2002, and 2013) were used to quantify the spatiotemporal dynamics of land-use change detection and examine the effect on hydrological response using Geographical Information System (GIS) and Soil and Water Assessment Tool (SWAT) model in the Genale watershed, Ethiopia. The model performance was evaluated through sensitivity, uncertainty analysis, calibration, and validation process. The analysis of LULC change patterns for the area under study over 24 years showed that most parts of the green forest, barren land, and range shrubs were changed into agriculture, built up, wetlands, and water body with an increase of agriculture by 60%, built up 68%, pasture 37%, range shrubs 9%, and water body 57% over (1990 to 2013), which increased surface runoff, water yield, and sediment yield in the catchment. Significant changes in hydrological elements were observed at the sub-basins scale, mainly associated with the uneven spatial distribution of LULC changes compared to the whole watershed. The impacts of individual LULC change on hydrological response show a good correlation matrix. The regional government needs to modify land development policies and sustainable plans for examining LULC change detection using satellite imagery to avoid illegal land expansion activities.