Non-perennial streams are widespread, critical to ecosystems and society, and the subject of ongoing policy debate. Prior large-scale research on stream intermittency has been based on long-term averages, generally using annually aggregated data to characterize a highly variable process. As a result, it is not well understood if, how, or why the hydrology of non-perennial streams is changing. Here, we investigate trends and drivers of three intermittency signatures that describe the duration, timing, and dry-down period of stream intermittency across the continental United States (CONUS). Half of gages exhibited a significant trend through time in at least one of the three intermittency signatures, and changes in no-flow duration were most pervasive (41% of gages). Changes in intermittency were substantial for many streams, and 7% of gages exhibited changes in annual no-flow duration exceeding 100 days during the study period. Distinct regional patterns of change were evident, with widespread drying in southern CONUS and wetting in northern CONUS. These patterns are correlated with changes in aridity, though drivers of spatiotemporal variability were diverse across the three intermittency signatures. While the no-flow timing and duration were strongly related to climate, dry-down period was most strongly related to watershed land use and physiography. Our results indicate that non-perennial conditions are increasing in prevalence over much of CONUS and binary classifications of ‘perennial’ and ‘non-perennial’ are not an accurate reflection of this change. Water management and policy should reflect the changing nature and diverse drivers of changing intermittency both today and in the future.