Quantification of hydrologic model prediction uncertainty for various flow quantiles is of great importance for water resource planning and management. Thus, this study is designed to assess the effect of subbasin spatial scale on the hydrological model prediction uncertainty for different flow quantiles. The Soil Water Assessment Tool (SWAT), a geographic information system (GIS) interfaced hydrological model, was used in this study. Here, the spatial variations within the sub-basins of the Omo Gibe River basin in Ethiopia’s Abelti, Wabi, and Gecha watersheds from 1989 to 2020 were examined. The results revealed that (1) for the Abelti, Wabi, and Gecha watersheds, SWAT was able to reproduce the observed hydrograph with more than 85%, 82%, and 73% accuracy in terms of the Nash-Sutcliffe efficiency coefficient (NSE), respectively; (2) the variation in the spatial size of the subbasin had no effect on the overall flow simulations. However, the reproduction of the flow quantiles was considerably influenced by the subbasin spatial scales; (3) the coarser subbasin spatial scale resulted in the coverage of most of the observations. However, the finer subbasin spatial scale provided the best simulation closer to the observed stream flow pattern; (4) the SWAT model performed much better in recreating moist, high, and very-high flows than it did in replicating dry, low, and very-low flows in the studied watersheds; (5) a smaller subbasin spatial scale (towards to distributed model) may better replicate low flows, while a larger subbasin spatial scale (towards to lumped model) enhances high flow replication precision. Thus, it is crucial to investigate the subbasin spatial scale to reproduce the peak and low flows; (6) in this study, the best subbasin spatial scales for peak and low flows were found to be 79–98% and 29–42%, respectively. Hence, it is worthwhile to investigate the proper subbasin spatial scales in reproducing various flow quantiles toward sustainable management of floods and drought.