This study combined a catchment model and one-dimensional lake model (GLM-AED) to simulate the response of hydrodynamics and water quality of subtropical Advancetown Lake (South-East Queensland, Australia) to future changing climates from 2040 to 2069 and 2070 to 2099 under Representative Concentration Pathway (RCP) 4.5 and 8.5 and increased water demand from a 50% increase in population over current levels. The simulation adequately reproduced water temperature (RMSE of 0.6 °C), dissolved oxygen (DO) (RMSE of 2 mg/L), and other water quality variables, such as nitrogen, phosphorus, and chlorophyll a (Chl-a). Warming temperatures dominated the change in thermal structure and hydrodynamic status of the lake under future climate change conditions. Projected changes in precipitation and hydrological response from the upstream catchment might, however, partly offset the warming temperatures under future climate change. Increased water withdrawal due to population growth, which involved water extraction from the epilimnion, showed antagonistic effects on water stability compared to those from climate change. Under a high emission scenario of RCP8.5 during the 2080s, there is an increased likelihood of winter turnover failure in Advancetown Lake. Nutrient concentrations were simulated to decrease from reduced catchment loads under future climate change conditions. However, Chl-a concentrations were simulated to increase, especially during the period after winter turnover, under these future conditions. The depth of the hypoxia front during stratification is expected to decrease and move towards the water surface, attributable to the warming water temperatures and prolonged thermal stratification, which might affect biogeochemical processes and exchange fluxes between the hypolimnion and bottom sediments. These potential changes may present challenges for water resource management under future conditions of climate change and population growth.