Highly fractionated granitoids are closely associated with Rb mineralization, yet the mechanisms that control Rb enrichment and details about the enrichment process have not been well constrained. The Guobaoshan Rb deposit in eastern Tianshan, NW China, is one of the largest granite-related Rb deposits; it preserves a series of gradual lithofacies ranging from biotite granite and muscovite granite to Rb-rich amazonite granite and pegmatite, and provides an excellent opportunity to constrain the Rb enrichment processes in granitic systems. The large Guobaoshan Rb deposit hosts 281,000 tons of Rb2O at a grade of 0.12% mainly in its amazonite-bearing granite and amazonite granite lithofacies. In this contribution, we integrate geochronology, bulk-rock geochemistry, and analysis of Nd and zircon Hf isotopes to characterize the evolution of the Guobaoshan granitic pluton and the mechanisms that generated Rb enrichment. The zircon U-Pb age of the biotite granite and columbite U-Pb age of the amazonite granite are 244.8 ± 1.8 Ma (1σ, mean square of weighted deviates [MSWD] = 1.1) and 241.9 ± 2.3 Ma (1σ, MSWD = 1.0), respectively. In situ Rb-Sr analysis of orthoclase, mica, and albite from the amazonite-bearing granite, amazonite granite, and pegmatite yields ages of 249.1 ± 7.3 Ma (2σ, MSWD = 1.6), 245.5 ± 16.8 Ma (2σ, MSWD = 0.63), and 245.8 ± 9.8 Ma (2σ, MSWD = 3.3), respectively. Together, these ages demonstrate that the Guobaoshan granitic pluton formed during the Triassic and underwent a protracted magmatic evolution. The Guobaoshan granitic pluton is characterized by high concentrations of SiO2, alkalis, and Al2O3, and low concentrations of MgO, Fe2O3, CaO, P2O5, and TiO2, with an Al saturation index (A/CNK) of 1.01−1.14. It is enriched in Rb, but depleted in Ba, Sr, P, and Eu, has low total rare earth element (REE) contents (83.1−221 ppm), and is characterized by significantly negative anomalies (Eu/Eu* = 0.01−0.44). The biotite granite is enriched in light rare earth elements (LREEs), whereas the muscovite granite, amazonite-bearing granite, amazonite granite, and pegmatite are depleted in LREEs, and exhibit a marked tetrad effect (TE1.3 = 1.05−1.50). These geochemical characteristics, combined with the non-CHARAC (charge-radius−controlled) ratios of Zr/Hf, Nb/Ta, Y/Ho, and K/Rb, are indicative of melt-fluid interaction during the evolution of the Guobaoshan magma. Given that the biotite granite is the least-evolved rock, its petrological and geochemical characteristics suggest that it is an I-type granite. The slightly variable εHf(t) and consistently negative εNd(t) values indicate that the magma from which the Guobaoshan granitic pluton crystallized was likely sourced from the Mesoproterozoic crust, with limited mantle contributions. The coeval ages and coherent geochemical variations and mineral compositions of these rocks suggest that they formed via fractional crystallization of plagioclase, mica, quartz, and K-feldspar in the same magmatic system. This is supported by fractional crystallization simulations using the rhyolite-MELTS software package. Based on the petrological, mineralogical, and geochemical characteristics of the muscovite granite, amazonite-bearing granite, amazonite granite, and pegmatite, as well as simulations using rhyolite-MELTS, high degrees of fractional crystallization of granitic magma and interaction of this evolving magma with F-rich fluids are suggested to have been the key mechanisms that caused enrichment of Rb, while the melt-fluid interaction was more critical for Rb mineralization.