This paper introduces a dataset containing consistent time-series measurements of anthropogenic activities potentially affecting stream quality across the conterminous United States and summarizes the most noteworthy trends from 61 variables in 16 categories. Data include measures of atmospheric deposition, agricultural production, livestock, urbanization, irrigation, land use, nutrients from fertilizer, dams/reservoirs, and pesticide use, among others. The trend periods range from 10 to 40 years, beginning as early as 1970 and ending in 2012. Detailed summaries are provided for 1992-2012. Key results include: increase of urbanization and ‘exurbanization’, particularly in the South, Southwest, and Mid-Atlantic; increases in crop production and fertilizer use in much of the Midwest; increases in the concentration of livestock, particularly of hogs and pigs; increases in irrigation, dams, and reservoirs in the Lower Mississippi and Lower Missouri watersheds, widespread increase in the use of the pesticide glyphosate; and widespread decrease in atmospheric deposition of sulfate. These results and others provide a framework for evaluating potential causes of water-quality changes over the past four decades.