Oysters are important estuarine species, providing numerous ecosystem services, including habitat and filtration. However, natural oyster reefs are declining, largely due to increased coastal development, habitat loss, and water-quality degradation. Despite these declines, little attention is given to understanding the natural stressors experienced by oysters. In Southwest Florida, reefs are predominantly intertidal, exposing oysters to a suite of stressors that may interact to decrease fitness. Yet, spatial and temporal variation in these natural environments is largely understudied. To fill this gap, we monitored five oyster reefs (Crassostrea virginica) across Estero Bay, FL, over two years, measuring oyster performance alongside numerous environmental factors. Oyster condition varied within reefs, among neighboring reefs, and across the estuary, but no single environmental variable consistently explained these patterns. Neighboring reefs separated by only hundreds of meters differed in oyster condition and live cover despite similar water-quality conditions, corresponding instead with fine-scale differences in reef elevation. Across the estuary, the influence of reef elevation was context dependent: greater exposure was associated with favorable oyster condition at one site but increased thermal exposure and reduced live cover at another. Oysters exposed to chronic low salinity also maintained condition and growth comparable to reefs experiencing more moderate salinity regimes, suggesting an important role of environmental history. Collectively, these findings demonstrate that oyster performance emerges from interacting physical and environmental processes operating across multiple scales. Reef-scale morphology, hydrodynamics, and biologically relevant measures of environmental variability may therefore provide more informative indicators of reef condition than broad environmental averages alone.