In the world's rivers, alteration of flow is a major driver of biodiversity decline. Global warming is now affecting the thermal and hydrological regimes of rivers, compounding the threat and complicating conservation planning. To inform management under a non-stationary climate, we must improve our understanding of how flow and thermal regimes interact to affect the population dynamics of riverine biota. We used long-term growth biochronologies, spanning 34 years and 400,000 km2, to model the growth dynamics of a long-lived, apex predator (Murray cod) as a function of factors extrinsic (river discharge; air temperature; sub-catchment) and intrinsic (age; individual) to the population. Annual growth of Murray cod showed significant, curvilinear, life-stage-specific responses to an interaction between annual discharge and temperature. Growth of early juveniles (age 1+ and 2+ years) exhibited a unimodal relationship with annual discharge, peaking near median annual discharge. Growth of late juveniles (3+ to 5+) and adults (>5+) increased with annual discharge, with the rate of increase being particularly high in adults, whose growth peaked during years with flooding. Years with very low annual discharge, as experienced during drought and under high abstraction, suppress growth rates of all Murray cod life-stages. Unimodal relationships between growth and annual temperature were evident across all life stages. Contrary to expectations of the Temperature Size Rule, the annual air temperature at which maximum growth occurred increased with age. The stage-specific response of Murray cod to annual discharge indicates that no single magnitude of annual discharge is optimal for cod populations, adding further weight to the case for maintaining and/or restoring flow variability in riverine ecosystems. With respect to climate change impacts, on balance our results indicate that the primary mechanism by which climate change threatens Murray cod growth is through alteration of river flows, not through warming annual mean temperatures per se.