Using daily discharge data from the USGS, we analyzed how hydrologic regimes vary with land use in four large hydrologic regions that span a gradient of natural land cover and precipitation across the continental United States. In each region we identified small streams (contributing area < 282 km2) that have continuous daily streamflow data. Using a national database, we characterized the composition of land cover of the watersheds in terms of aggregate measures of agriculture, urbanization, and least disturbed (“natural”). We calculated hydrologic alteration using 10 ecologically-relevant hydrologic metrics that describe magnitude, frequency, and duration of flow for 158 watersheds within the Southeast (SE), Central (CE), Pacific Northwest (NW), and Southwest (SW) hydrologic regions of the United States. Within each watershed, we calculated percent cover for agriculture, urbanized land, and least disturbed land to elucidate how components of the natural flow regime inherent to a hydrologic region is modified by different types and proportions of land cover. We also evaluated how dams in these regions altered the hydrologic regimes of the 43 streams that have pre- and post-dam daily streamflow data. In an analysis of flow alteration along gradients of increasing proportion of the three land cover types, we found many regional differences in hydrologic responses. In response to increasing urban land cover, peak flows increased (SE and CE), minimum flows increased (CE) or decreased (NW), duration of near-bankfull flows declined (SE, NW) and flow variability increased (SE, CE, and NW). Responses to increasing agricultural land cover were less pronounced, as minimum flows decreased (CE), near-bankfull flow durations increased (SE and SW), and flow variability declined (CE). In a second analysis, for three of the regions, we compared the difference between least disturbed watersheds and those having either > 15% urban and > 25% agricultural land cover. Relative to natural land cover in each region, urbanization either increased (SE and NW) or decreased (SW) peak flows, decreased minimum flows (SE, NW, and SW), decreased durations of near-bankfull flows (SE, NW, and SW), and increased flow variability (SE, NW, and SW). Agriculture had similar effects except in the SE, where near-bankfull flow durations increased. Overall, urbanization appeared to induce greater hydrologic responses than similar proportions of agricultural land cover in watersheds. Finally, the effects of dams on hydrologic variation were largely consistent across regions, with a decrease in peak flows, an increase in minimum flows, an increase in near-bankfull flow durations, and a decrease in flow variability. We use this analysis to evaluate the relative degree to which land use has altered flow regimes across regions in the US with naturally varying climate and natural land cover, and we discuss the geomorphic and ecological implications of such flow modification. We end with a consideration of what elements will ultimately be required to conduct a more comprehensive national assessment of the hydrologic responses of streams to land cover types and dams. These include improved tools for modeling hydrologic metrics in ungauged watersheds, incorporation of high-resolution geospatial data to map geomorphic and hydrologic drivers of stream response to different types of land cover, and analysis of scale dependence in the distribution of land-use impacts, including mixed land uses. Finally, ecological and geomorphic responses to human alteration of land cover will have to be calibrated to the regional hydroclimatological, geologic, and historical context in which the streams occur, in order to determine the degree to which stream responses are region-specific versus geographically independent and broadly transferable.