Anthropogenic changes in temperature and stream flow, associated with watershed land use and climate change, are critical influences on the distribution and abundance of riverine fishes. To project the effects of changing land use and climate, we modeled a smallmouth bass (Micropterus dolomieu) population in a midwestern USA, large river–floodplain ecosystem under historical (1915–1925), present (1977–1990), and future (2060, influenced by climate change) temperature and flow regimes. The age-structured model included parameters for temperature and river discharge during critical seasonal periods, fish population dynamics, and fishing harvest. Model relationships were developed from empirical field data collected over a 13-yr period. Sensitivity analyses indicated that discharge during the spawning/rearing period had a greater effect on adult density and fishing yield than did spawning/rearing temperature or winter discharge. Simulations for 100 years projected a 139% greater mean fish density under a historical flow regime (64.9 fish/ha) than that estimated for the present (27.1 fish/ha) with a sustainable fishing harvest under both flow regimes. Simulations under future climate-change-induced temperature and flow regimes with present land use projected a 69% decrease in mean fish density (8.5 fish/ha) from present and an unstable population that went extinct during 56% of the simulations. However, when simulated under a future climate-altered temperature and flow regime with historical land use, the population increased by 66% (45.0 fish/ha) from present and sustained a harvest. Our findings suggest that land-use changes may be a greater detriment to riverine fishes than projected climate change and that the combined effects of both factors may lead to local species extinction. However, the negative effects of increased temperature and precipitation associated with future global warming could be mitigated by river channel, floodplain, and watershed restoration.