Over half of global rivers and streams lack perennial flow, and understanding the distribution and drivers of their flow regimes is critical for understanding their hydrologic, biogeochemical, and ecological functions. We analyzed nonperennial flow regimes using 540 U.S. Geological Survey watersheds across the contiguous United States from 1979 to 2018. Multivariate analyses revealed regional differences in no-flow fraction, date of first no flow, and duration of the dry-down period, with further divergence between natural and human-altered watersheds. Aridity was a primary driver of no-flow metrics at the continental scale, while unique combinations of climatic, physiographic and anthropogenic drivers emerged at regional scales. Dry-down duration showed stronger associations with nonclimate drivers compared to no-flow fraction and timing. Although the sparse distribution of nonperennial gages limits our understanding of such streams, the watersheds examined here suggest the important role of aridity and land cover change in modulating future stream drying. Plain Language Summary A majority of global streams are nonperennial, flowing only part of the year, and are critical for sustaining flow downstream, providing habitat for many organisms, and regulating chemical and biological processes. Using long-term U.S. Geological Survey measurements for 540 watersheds across the contiguous United States, we mapped patterns and examined the causes of no-flow fraction, the fraction of each climate year with no flow, no-flow timing, the date of the climate year on which the first recorded no flow takes place, and length of the dry-down period, the average number of days from a local peak in daily flow to the first occurrence of no flow. We found differences in patterns of no-flow characteristics between regions, with higher no-flow fraction, earlier timing, and shorter dry-down duration in the western United States. No-flow fractions were greater and less variable in natural watersheds, while no-flow timing was earlier and dry-down duration was shorter in human-modified watersheds. Aridity had the greatest effect on intermittence across the United States, but unique combinations of climate, biophysical, and human impacts were important in different regions. The number of gages measuring streamflow in nonperennial streams is small compared to perennial streams, and increased monitoring is needed to better understand drying behavior. Key Points . Three metrics reveal regional and human-driven patterns of nonperennial flow: no-flow fraction, day of first no flow, and dry-down duration Streams with human modifications generally dry more quickly than unmodified streams, especially in California and the Southern Great Plains Climate strongly influences no-flow fraction and timing, but physiographic variables are more important for the duration of dry down