Condition indices are key predictors of health and fitness in wild fish populations. Variation in body condition, therefore, can be used to identify stressful conditions that may impact endangered species, such as California’s endemic Delta Smelt (Hypomesus transpacificus McAllister, 1963). Here, we examined spatiotemporal variation in the condition indices of > 1600 Delta Smelt collected over nine years (2011–2019), a period characterized by tremendous variability in hydrodynamic and water quality conditions. The population exhibited low hepatosomatic index (HSI) and condition factor (CF) during September/October/November (fall), and both condition indices declined over the nine-year study during fall. HSI was positively correlated with indicators of pelagic productivity (e.g., Chlorophyll a, zooplankton biomass, and proximity to tidal wetlands), whereas CF was negatively correlated with temperature, peaking at a relatively cool 10–13 °C. In sum, seasonal and interannual variation in body condition corresponded most strongly with pelagic productivity and water temperature, with little correlation to freshwater outflow. Management actions that increase pelagic productivity, restore and freshen productive wetlands during late summer-fall, and reduce water temperatures overall are likely to benefit condition indices and, therefore, fitness of the Delta Smelt population.