Abstract Intermittent streams that cease to flow during dry periods represent more than half of the global river network, and are particularly common in arid and semi‐arid regions. They are characterised by high spatial and temporal variability in aquatic habitat, forming a shifting habitat mosaic that supports diverse assemblages of native and endemic species. Climate projections for much of the world predict greater variation in precipitation and increasing drought severity, suggesting a need to better understand species' responses to habitat variability within intermittent stream ecosystems. Here we explored changes in the distribution and abundance of aquatic vertebrates in response to a wide range of annual hydrologic conditions within a Mediterranean‐climate intermittent stream in California. We conducted wetted habitat and vertebrate abundance surveys during the dry season for 7 years, spanning both extreme wet and extreme dry annual precipitation conditions, and characterised the variation in the size, persistence, and spatial configuration of wetted habitats in relation to the observed abundance and composition of fishes, amphibians, and aquatic reptiles. We characterised the habitat mosaic using a k‐means clustering approach, and identified three habitat types with distinct size, persistence, and connectivity distributions. We found that some wetted habitat units persisted across all years, regardless of antecedent precipitation, whereas others dried in all but the wettest years. We determined that persistent pools, a subset of wetted habitats present in the stream, supported diverse assemblages of native species even during extreme dry conditions, while transient pools acted as important habitat for particular species and life stages, including a young‐of‐year minnow species. Linear mixed models indicated that species' abundances were influenced by habitat quantity, quality, and connectivity. Our study ‐ considers intermittent streams as shifting habitat mosaics and uses multi‐year surveys to understand the ecological consequences of habitat variability within and across years to advance our understanding of intermittent stream ecology and the implications of climate change for spatial and temporal patterns of refuge habitat.