Zuogong County is located in the southeast of Tibet, which is rich in hot spring geothermal resources, but its development and utilization degree are low, and the genetic mechanism of the geothermal system is not clear. Hydrogeochemical characteristics of geothermal water are of great significance in elucidating the genesis and evolution of geothermal systems, as well as the sustainable development and utilization of geothermal resources. The hydrogeochemical characteristics and genesis of the geothermal water in Zuogong County were investigated using hydrogeochemical analysis, a stable isotope (δD, δ18O) approach, and an inverse simulation model for water–rock reactions using the PHREEQC. The results indicated that the Zuogong geothermal system is a deep circulation heating type without a magmatic heat source. The chemical types present in the geothermal water from the Zuogong area are HCO3 and HCO3·SO4, and the main cations are Na+ and Ca2+. The groundwater is replenished by atmospheric precipitation and glacier meltwater. The salt content of geothermal water mainly comes from the interaction between water and surrounding rocks during the deep circulation process. The reservoir temperature of geothermal water in Zuogong is 120–176 °C before mixing with non-geothermal water and drops to 62–98 °C after mixing with 58 to 79% of non-geothermal water. According to the proposed conceptual model, geothermal water mainly produces water–rock interaction with aluminosilicate minerals in the deep formation, while in shallow areas it interacts mainly with sulfate minerals. These findings contribute to a better understanding of the geothermal system in Zuogong County, Tibet.