It is widely known that watershed hydrology is dependent on many factors, including land use, climate, and soil conditions. But the relative impacts of different types of land use on the surface water are yet to be ascertained and quantified. This research attempted to use a comprehensive approach to examine the hydrologic effects of land use at both a regional and a local scale. Statistical and spatial analyses were employed to examine the statistical and spatial relationships of land use and the flow and water quality in receiving waters on a regional scale in the State of Ohio. Besides, a widely accepted watershed-based water quality assessment tool, the Better Assessment Science Integrating Point and Nonpoint Sources (BASINS), was adopted to model the plausible effects of land use on water quality in a local watershed in the East Fork Little Miami River Basin. The results from the statistical analyses revealed that there was a significant relationship between land use and in-stream water quality, especially for nitrogen, phosphorus and Fecal coliform. The geographic information systems (GIS) spatial analyses identified the watersheds that have high levels of contaminants and percentages of agricultural and urban lands. Furthermore, the hydrologic and water quality modeling showed that agricultural and impervious urban lands produced a much higher level of nitrogen and phosphorus than other land surfaces. From this research, it seems that the approach adopted in this study is comprehensive, covering both the regional and local scales. It also reveals that BASINS is a very useful and reliable tool, capable of characterizing the flow and water quality conditions for the study area under different watershed scales. With little modification, these models should be able to adapt to other watersheds or to simulate other contaminants. They also can be used to study the plausible impacts of global environmental change. In addition, the information on the hydrologic effects of land use is very useful. It can provide guidelines not only for resource managers in restoring our aquatic ecosystems, but also for local planners in devising viable and ecologically-sound watershed development plans, as well as for policy makers in evaluating alternate land management decisions.