Natural and anthropogenic factors influence water-quality conditions in the Yellowstone River Basin. Physiography parallels the structural geologic setting that is generally composed of several uplifts and structural basins. Contrasts in climate and vegetation reflect topographic controls and the midcontinental location of the study unit. Surface-water hydrology reflects water surpluses in mountainous areas that are dominated by snowmelt runoff, and arid to semiarid conditions in the plains that are dissected by typically irrigated valleys in the remainder of the study unit. Principal shallow aquifers are Tertiary sandstones and unconsolidated Quaternary deposits. Human population, though sparsely distributed in general, is growing most rapidly in a few urban centers and resort areas, mostly in the northwestern part of the basin. Land use is areally dominated by grazing in the basins and plains and economically dominated by mineral-extraction activities. Forests are the dominant land cover in mountainous areas. Cropland is a major land use in principal stream valleys. Water use is dominated by irrigated agriculture overall, but mining and public-supply facilities are major users of ground water. Coal and hydrocarbon production and reserves distinguish the Yellowstone River Basin as a principal energy-minerals resources region. Current metallic ore production or reserves are nationally significant for platinum-group elements and chromium.The study unit was subdivided as an initial environmental stratification for use in designing the National Water-Quality Assessment Program investigation that began in 1997. Ecoregions, geologic groups, mineral-resource areas, and general land-cover and land-use categories were used in combination to define 18 environmental settings in the Yellowstone River Basin. It is expected that these different settings will be reflected in differing water-quality or aquatic-ecological characteristics.