In recent decades, the depletion of surface water resources within the Lake Urmia Basin (LUB), Iran, has emerged as a significant environmental concern. Both anthropogenic activities and climate change have influenced the availability and distribution of surface water resources in this area. This research endeavors to provide a comprehensive evaluation of the impacts of climate change and anthropogenic activities on surface water resources across the LUB. Various critical climatic and anthropogenic factors affecting surface water bodies, such as air temperature (AT), cropland (CL), potential evapotranspiration (PET), snow cover, precipitation, built-up areas, and groundwater salinity, were analyzed from 2000 to 2021 using the Google Earth Engine (GEE) cloud platform. The JRC-Global surface water mapping layers V1.4, with a spatial resolution of 30 m, were employed to monitor surface water patterns. Additionally, the Mann–Kendall (MK) non-parametric trend test was utilized to identify statistically significant trends in the time series data. The results reveal negative correlations of −0.56, −0.89, −0.09, −0.99, and −0.79 between AT, CL, snow cover, built-up areas, and groundwater salinity with surface water resources, respectively. Conversely, positive correlations of 0.07 and 0.12 were observed between precipitation and PET and surface water resources, respectively. Notably, the findings indicate that approximately 40% of the surface water bodies in the LUB have remained permanent over the past four decades. However, there has been a loss of around 30% of permanent water resources, transitioning into seasonal water bodies, which now account for nearly 13% of the total. The results of our research also indicate that December and January are the months with the most water presence over the LUB from 1984 to 2021. This is because these months align with winter in the LUB, during which there is no water consumption for the agriculture sector. The driest months in the study area are August, September, and October, with the presence of water almost at zero percent. These months coincide with the summer and autumn seasons in the study area. In summary, the results underscore the significant impact of human activities on surface water resources compared to climatic variables.