The Gejiu ore district (~ 3.2 Mt Sn) is located in eastern Yunnan Province, southwest China, and is one of the largest Sn polymetallic ore districts in the world. Athough it has been widely studied, the petrogenesis of ore-related granites is still unclear. In this paper, we present petrological, geochemical, and geochronological data on the granites associated with the Kafang Cu–Sn deposit in the Gejiu ore district (65 Mt Cu ore at a grade of 1.2% and 32 Mt Sn ore at a grade of 0.6%). We use these data to constrain the source, evolution, oxygen fugacity, and tectonic setting of the granitic magmatism. Zircon U–Pb dating yielded an age of 82.8 ± 0.6 Ma for the Kafang granite. The high zircon δ¹⁸O values (7.45–9.74‰; mean = 8.80‰) and narrow range of ε_Nd(t) values (–9.0 to –7.7) of the Kafang granite indicate a highly evolved S-type granite derived by partial melting of metamorphic basement rocks of the Jiangnan orogenic belt. Rayleigh fractional crystallization modeling, along with the increase in Hf and Sn contents and decrease in Eu/Eu* values of zircons, record extensive fractional crystallization, and Sn enrichment during magmatic evolution. The Kafang granite was relatively reduced, as evidenced by low zircon Ce/Ce* (10.0–366; mean = 171), (Ce/Nd)_N (0.76–8.32; mean = 4.41), △FMQ (–2.5 to 1.2) values, and Fe³⁺-depleted biotite compositions (Fe³⁺/(Fe³⁺ + Fe²⁺) = 0–0.10), which were favorable for Sn mineralization but not for Cu mineralization. Copper in the Kafang deposit may not have been derived from the granite. Our results suggest that biotite and zircon geochemical compositions, particularly biotite Mg# and A/CNK values and zircon Hf contents, Eu anomalies, and Ce/Ce^* and (Ce/Nd)_N ratios, are robust tracers of different types of magmatic-hydrothermal ore deposits (i.e., Cu, Mo, W, and Sn). Late Cretaceous magmatism in the Gejiu region and other areas along the southern margin of South China formed an E–W-trending igneous belt that was likely related to northward subduction of the Neo-Tethyan plate rather than northwestward subduction of the Paleo-Pacific plate.