Changes in the position of the low salinity zone, a habitat suitability index, turbidity, and water temperature modeled from four 100-year scenarios of climate change were evaluated for possible effects on delta smelt Hypomesus transpacificus, which is endemic to the Sacramento–San Joaquin Delta. The persistence of delta smelt in much of its current habitat into the next century appears uncertain. By mid-century, the position of the low salinity zone in the fall and the habitat suitability index converged on values only observed during the worst droughts of the baseline period (1969–2000). Projected higher water temperatures would render waters historically inhabited by delta smelt near the confluence of the Sacramento and San Joaquin rivers largely uninhabitable. However, the scenarios of climate change are based on assumptions that require caution in the interpretation of the results. Projections like these provide managers with a useful tool for anticipating long-term challenges to managing fish populations and possibly adapting water management to ameliorate those challenges.