Increasing evidence shows that the mantle contributes (directly or indirectly) to Sn-bearing granites worldwide. However, the specific role of mantle in the formation of tin granites and related mineralization remains poorly understood. In the world-class Dachang district, South China, tin mineralization is related to the Longxianggai equigranular/porphyritic biotite granites and tin orebodies are cut by granite porphyry dykes hosting mafic microgranular enclaves (MMEs). A combination of zircon U-Pb dating and Hf-O isotopes, mineral chemistry, and whole-rock elemental and Sr-Nd isotopic compositions—for granitic rocks and MMEs, is employed to constrain the petrogenesis and to unravel the link between tin fertility and mantle upwelling. Laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) zircon U-Pb dating indicates that the biotite granites were emplaced at ca. 93 Ma, and the granite porphyry dykes and MMEs were formed at ca. 86 Ma. The biotite granites are silica- and alkali-enriched with A/CNK ratios of 1.04–1.36, and exhibit elevated concentrations of Li, F, P, Rb, Cs, Ta, Sn, W, and U, showing affinities with highly fractionated S-type granites. Whole-rock geochemical and Nd isotopic (εNd(t) = −10.0 to −7.8) data, and in situ zircon Hf-O (εHf(t) = −9.9 to −3.9, δ18O = 6.2–8.9‰) isotopes indicate that the biotite granites were formed by partial melting of metasedimentary rocks at relatively high temperatures (≥782 °C), possibly with minor input of mantle material. Likewise, the post-ore granite porphyry dykes have similar chemical and mineralogical characteristics as fractionated S-type granites. Zircon Hf-O isotopes (εHf(t) = −9.0 to −4.9, δ18O = 6.5–8.2‰) and whole-rock geochemical data suggest they were derived from a similar source as the biotite granites, whereas elevated εNd(t) values of −5.0 to −3.3 for granite porphyry dykes relative to biotite granites reveal an increasing mantle input. Distinct εNd(t) (−0.4 and −0.3) and zircon Hf-O (εHf(t) = 1.5–5.0, δ18O = 6.5–7.2‰) isotopes of the MMEs, suggest that the mafic melt could be sourced from the asthenospheric mantle, contaminated by subcontinental lithospheric mantle/continental crust during magma ascent, and hybridized by felsic melt at emplacement-level. The magmatic sequence in the Dachang district is indicative of an extensional tectonic setting where mantle-derived magmas are predicted to migrate to shallower crustal levels as the crust progressively becomes thinner and hotter. High-temperature partial melting of mature metasedimentary crust triggered by heat input from the upwelled mantle, may contribute to biotite breakdown, which is important for concentrating tin in melts. Fractional crystallization of initially Sn-rich felsic melts under reduced conditions makes further tin enrichment and produces Sn-bearing granites (the Longxianggai pluton). Prolonged mantle upwelling results in distinct magma mixing and the formation of granite porphyry dykes and MMEs. These dykes are highly fractionated with elevated Sn and W contents, which show great potential to form hydrothermal Sn-W mineralization.