The assessment of Landuse and Landcover (LULC) changes on hydrology is essential for the development of sustainable water resource strategies. Specifically, understanding how change in each LULC class influences hydrological components will greatly improve predictability of hydrological consequences to LULC changes and thus can help stakeholders make better decisions. However, given the limited availability of digital LULC maps and simultaneous changes of multiple LULC classes, it is difficult to quantify impacts of change in individual LULC class on hydrology. In this study, an integrated approach of hydrological modeling and multiple regression analysis was applied to quantify contributions of changes for individual LULC classes on changes in hydrological components. As a case study, hydrological modeling was conducted for each of the LULC map in four time periods (1973, 1986, 1992, and 1997) in the upper San Pedro watershed using the Soil and Water Assessment Tool (SWAT). Changes in hydrological components between two simulations using LULC maps in 1997 and 1973, respectively, were related to changes of LULC in a multiple regression to quantify the effect of changes in LULC to that of hydrological components at the subbasinal scale. While urbanization was the strongest contributor to the increase of surface runoff and water yield from 1973 to 1997, replacement of desertscrub/grassland by mesquite was the strongest contributor to the decreased baseflow/percolation and contributed to the increased ET. Increased runoff, declined percolation, and increased ET have a negative impact on water resources in the upper San Pedro River Basin, thus urbanization and mesquite invasion seems to be major environmental stressors affecting local water resources. Our approach in quantifying the contributions of changes for individual LULC to hydrological components will provide quantitative information for stakeholders in planning and making decisions for land and water resource management. The approach to assess changes in surface hydrology could widely be applied to a variety of other watersheds, where time-sequenced digital LULC is available.