Thermal regime is strongly associated with hydrodynamics in water, and it plays an important role in the dynamics of water quality and ecosystem succession of stratified reservoirs. Changes in both climate and hydrological conditions can modify thermal regimes. Liuxihe Reservoir (23°45′50″N; 113°46′52″E) is a large, stratified and deep reservoir in Guangdong Province, located at the Tropic of Cancer of southern China. The reservoir is a warm monomictic water body with a long period of summer stratification and a short period of mixing in winter. The vertical distribution of suspended particulate material and nutrients are influenced strongly by the thermal structure and the associated flow fields. The hypolimnion becomes anoxic in the stratified period, increasing the release of nutrients from the bottom sediments. Fifty-one years of climate and reservoir operational observations are used here to show the marked changes in local climate and reservoir operational schemes. The data show increasing air temperature and more violent oscillations in inflow volumes in the last decade, while the inter-annual water level fluctuations tend to be more moderate. To quantify the effects of changes in climate and hydrological conditions on thermal structure, we used a numerical simulation model to create scenarios incorporating different air temperatures, inflow volumes, and water levels. The simulations indicate that water column stability, the duration of the mixing period, and surface and outflow temperatures are influenced by both natural factors and by anthropogenic factors such as climate change and reservoir operation schemes. Under continuous warming and more stable storage in recent years, the simulations indicate greater water column stability and increased duration of stratification, while irregular large discharge events may reduce stability and lead to early mixing in autumn. Our results strongly suggest that more attention should be focused on water quality in years of extreme climate variation and hydrological conditions, and selective withdrawal of deep water may provide an efficient means to reduce internal loading in warm years.