Stable Sn isotopes have been widely used to trace the planetary differentiation processes, the provenance and trade paths of ancient bronze artifacts, the mineralization history of tin ore deposits, and the terrestrial magmatic processes. However, systematic Sn isotope studies of felsic igneous rocks especially the Sn mineralization-related highly evolved granites are still lacking. In this study, we present the first high-precision Sn isotope data of two Sn-rich highly evolved S-type granites (Laochang and Kafang) from the world-class Gejiu Sn ore district. These granite samples show remarkably variable δ122/118Sn values (relative to the Sn standard solution NIST 3161a) ranging from 0.11 ± 0.02‰ to 0.93 ± 0.02‰ (2σ), which is the largest variation range reported in granites so far. The absence of correlations between Sn isotopes and LOI (loss-on-ignition) and εNd(t) values, along with the low magmatic oxygen fugacity (△FMQ < 0) for these granites, rule out hydrothermal alteration, wall-rock assimilation, source composition heterogeneity, and anatexis processes as causes of the Sn isotope fractionation. The Laochang granites show negative correlations between δ122/118Sn values and magmatic differentiation indicators (e.g., CaO, Fe2O3, Ti, Eu/Eu*, F/Cl), suggesting fractional crystallization increased the δ122/118Sn isotopes in the residual melts. The fractional crystallized minerals are mainly composed of biotite, plagioclase, and minor ilmenite. Compared with the Laochang granites, the Kafang granites show higher SiO2 contents, F/Cl ratios, and δ122/118Sn values, suggesting the magma at this stage was fluid-saturated and fluid exsolution coupled with fractional crystallization would further enrich the heavy Sn isotopes in the residual melts. We further quantified the contributions of crystal fractionation and fluid exsolution on Sn isotopic variability using a Rayleigh fractionation model. The modeling indicates that △122/118Sncrystal-melt = −0.6 to −0.5‰ and △122/118Snfluid-melt = −1.9 to −0.7‰ with an initial H2O content of 2 wt.% can explain the observed δ122/118Sn values of Gejiu granites. This study implies that both crystal fractionation and fluid exsolution processes cause increase of Sn isotopic values in the highly evolved granites and Sn isotopes are useful for tracing the evolution of highly differentiated igneous rocks.