Protecting hydrologic connectivity of freshwater ecosystems is fundamental to ensuring species persistence, ecosystem integrity, and human well-being. More frequent and severe droughts associated with climate change are poised to significantly alter flow intermittence patterns and hydrologic connectivity in dryland streams of the American Southwest, with deleterious effects on highly endangered fishes. By integrating local-scale hydrologic modeling with emerging approaches in landscape ecology, we quantify fine-resolution, watershed-scale changes in habitat size, spacing, and connectance under forecasted climate change in the Verde River Basin, United States. Model simulations project annual zero-flow day frequency to increase by 27% by midcentury, with differential seasonal consequences on continuity (temporal continuity at discrete locations) and connectivity (spatial continuity within the network). A 17% increase in the frequency of stream drying events is expected throughout the network with associated increases in the duration of these events. Flowing portions of the river network will diminish between 8% and 20% in spring and early summer and become increasingly isolated by more frequent and longer stretches of dry channel fragments, thus limiting the opportunity for native fishes to access spawning habitats and seasonally available refuges. Model predictions suggest that midcentury and late century climate will reduce network-wide hydrologic connectivity for native fishes by 6-9% over the course of a year and up to 12-18% during spring spawning months. Our work quantifies climate-induced shifts in stream drying and connectivity across a large river network and demonstrates their implications for the persistence of a globally endemic fish fauna.fragmentation | temporary streams | barriers | groundwater extraction R epresenting one of the most critically imperiled environments in the world (1), virtually every drop of water is managed, accounted for, and allocated for human use in arid ecosystems of the American Southwest (2). Ephemeral and intermittent streams (hereafter called "dryland streams") that fluctuate between drying and wetting are a distinguishing characteristic of these ecosystems and are associated with a range of important ecological and societal values (3). From a landscape perspective they provide essential hydrologic connectivity during bouts of stream inundation by linking a patchwork of perennial habitats over space and in time. Hydrologic connectivity-here referring to the upstream-downstream longitudinal connection of surface water-is widely recognized as a primary driver of freshwater ecosystem structure and function (3, 4) and is considered fundamental to organic matter and nutrient transport and the persistence of aquatic species by facilitating the repeated recolonization of motile and drifting organisms from isolated stream pools (refuges) to rewetted channel reaches that are intermittently dispersed throughout the river network (5, 6).Prospects of a rapidly changing climate that ...