The Three Rivers Lateral Collision Zone (TRLCZ), situated at the southeastern margin of the Tibetan Plateau, is a crucial frontier where materials from the plateau flow southeastward. This study extensively investigated the hydrochemical characteristics and origin of helium and carbon isotopes in 73 thermal springs within the TRLCZ. The analysis revealed dominant processes, including carbonate and silicate interactions, resulting in elevated concentrations of HCO3− and Na+. The impact of Ca/Mg-rich minerals, particularly dolomite, influenced the cation composition. Additionally, gypsum dissolution, notably in the Lancangjiang Fault and Weixi–Qiaohou Fault, was highlighted through Ca/SO4 ratios. The positive correlation between SO42− and Cl− indicated dilution by shallow cold water, explaining the lower SO42− content in the Jingshajiang–Zhongdian Fault and Nujiang Fault compared to the Weixi–Qiaohou Fault and Lancangjiang Fault. The circulation depth of thermal spring water varied, with the northern Weixi–Qiaohou Fault exhibiting the shallowest circulation depth (~3 km), while the Jingshajiang–Zhongdian Fault and southern segments of the Nujiang Fault displayed deeper depths—ranging from 4 to 7 km. A positive correlation between the circulation depth and fault activity was also observed. The Rc/Ra ratios of free gas samples, predominantly indicating crustal origin, varied from 0.01 Ra to 0.53 Ra. Elevated Rc/Ra ratios in the research area suggested potential minor additions of mantle helium through faults and fractures. Crustal limestone was identified as the primary source of CO2-rich samples, with δ13CCO2 values ranging from −1.6‰ to −7.2‰, while trace amounts of mantle CO2 were found. The spatial distribution of the H2 concentration, CO2 concentration, He concentration, and mantle He proportions in gases indicated that higher values of He concentration and mantle He% always occur near sampling points with deeper circulation depths. However, no similar correlation was observed for H2 and CO2. Most earthquakes of magnitude 5 or greater occurred near the regions with high values of mantle source He release, highlighting the critical role of mantle fluids in the occurrence of earthquakes in the region. In this study, a fluid circulation model was developed to describe the process of fluid (water and gas) circulation migration and earthquake generation in the TRLCZ.