Intra-annual patterns of hypoxia in Chesapeake Bay have been recorded since the mid-1900s, but anthropogenic inputs and climate change have exacerbated the volume and extent of hypoxic waters, which mobile marine fishes avoid. This estuary provides important habitat for many seasonally resident species but declines in relative abundance and relative habitat usage have been documented. An understanding of the relationship between environmental conditions and habitat suitability could assist in evaluating the stock status of these species. To characterize baseline habitat associations for Micropogonias undulatus, Leiostomus xanthurus, Paralichthys dentatus, and Cynoscion regalis, ecological niche models were developed relating catch-per-unit-effort data from a fisheries-independent trawl survey conducted within Chesapeake Bay to environmental covariates. Model output indicated that impacts of climate change on the environmental conditions, including continued increases in temperature and decreases in dissolved oxygen (DO) concentration, will likely further the decline in estuarine utilization of these species. The niche envelopes were then paired with hindcasts from an estuarine-carbon-biogeochemical regional model to derive estimates of spatiotemporal habitat suitability. The patterns in habitat suitability do not match those of declining abundance, indicating that dynamics outside of Chesapeake Bay are likely driving the shift. An auxiliary model was used to replace hypoxic DO concentrations with normoxic concentrations to evaluate the influence of hypoxia on habitat suitability. Both hypoxic severity and extent displayed significant associations with the quantity of suitable habitat available to each species in the bay. Results characterize the complexity of the dynamics underpinning observed trends in habitat utilization.