The components of water balance (WBC) that involve precipitation, evapotranspiration, runoff, irrigation, and groundwater recharge are critical for understanding the hydrological cycle and water management of resources in semi-arid and arid areas. This paper assesses temporal and spatial distributions of surface runoff, actual evapotranspiration, and groundwater recharge upstream of the New Assiut Barrage (NAB) in the Nile Valley, Upper Egypt, using the WetSpass-M model for the period 2012–2020. Moreover, this study evaluates the effect of land cover/land use (LULC) alterations in the study period on the WBC of the NAB. The data provided as input for the WetSpass-M model in the structure of raster maps using the Arc-GIS tool. Monthly meteorological factors (e.g., temperature, rainfall, and wind speed), a digital elevation model (DEM), slope, land cover, irrigation cover, a soil map, and depth to groundwater are included. The long-term temporal and spatial mean monthly irrigation and precipitation (127 mm) is distributed as 49% (62 mm) actual evapotranspiration, 15% (19 mm) groundwater recharge, and 36% (46 mm) surface runoff. The replacement of cropland by built-up areas was recognized as the primary factor responsible for the major decrease in groundwater, an increase in evapotranspiration and an increase in surface runoff between LCLU in 2012 and 2020. The integration of the WetSpass model with GIS has shown its effectiveness as a powerful approach for assessing WBC. Results were more accurate and reliable when hydrological modeling and spatial analysis were combined. The results of this research can help make well-informed decisions about land use planning and sustainable management of water resources in the upstream area of the NAB.