Longer, drier summers projected for arid and semi-arid regions of western North America under climate change are likely to have enormous consequences for water resources and river-dependent ecosystems. Many climate change scenarios for this region involve decreases in mean annual streamflow, late summer precipitation and late-summer streamflow in the coming decades. Intermittent streams are already common in this region, and it is likely that minimum flows will decrease and some perennial streams will shift to intermittent flow under climate-driven changes in timing and magnitude of precipitation and runoff, combined with increases in temperature. To understand current intermittency among streams and analyze the potential for streams to shift from perennial to intermittent under a warmer climate, we analyzed historic flow records from streams in the Upper Colorado River Basin (UCRB). Approximately two-thirds of 115 gaged stream reaches included in our analysis are currently perennial and the rest have some degree of intermittency. Dry years with combinations of high temperatures and low precipitation were associated with more zero-flow days. Mean annual flow was positively related to minimum flows, suggesting that potential future declines in mean annual flows will correspond with declines in minimum flows. The most important landscape variables for predicting low flow metrics were precipitation, percent snow, potential evapotranspiration, soils, and drainage area. Perennial streams in the UCRB that have high minimum-flow variability and low mean flows are likely to be most susceptible to increasing streamflow intermittency in the future.