Hydrothermally altered bedrock in the Silverton mining area, southwest Colorado, USA, contains sulfide minerals that weather to produce acidic and metal-rich leachate that is toxic to aquatic life. This study utilized a geographic information system (GIS) and statistical approach to identify watershed-scale geologic variables in the Silverton area that influence water quality. GIS analysis of mineral maps produced using remote sensing datasets including Landsat Thematic Mapper, advanced spaceborne thermal emission and reflection radiometer, and a hybrid airborne visible infrared imaging spectrometer and field-based product enabled areas of alteration to be quantified. Correlations between water quality signatures determined at watershed outlets, and alteration types intersecting both total watershed areas and GIS-buffered areas along streams were tested using linear regression analysis. Despite remote sensing datasets having varying watershed area coverage due to vegetation cover and differing mineral mapping capabilities, each dataset was useful for delineating acid-generating bedrock. Areas of quartz–sericite–pyrite mapped by AVIRIS have the highest correlations with acidic surface water and elevated iron and aluminum concentrations. Alkalinity was only correlated with area of acid neutralizing, propylitically altered bedrock containing calcite and chlorite mapped by AVIRIS. Total watershed area of acid-generating bedrock is more significantly correlated with acidic and metal-rich surface water when compared with acid-generating bedrock intersected by GIS-buffered areas along streams. This methodology could be useful in assessing the possible effects that alteration type area has in either generating or neutralizing acidity in unmined watersheds and in areas where new mining is planned.