The Kunduleng granite hosts one of several significant uranium anomalies within the southern Great Xing’an Range, NE China. Whole-rock geochemistry and mineral chemistry data, along with the zircon U-Pb-Hf isotope have been used to constrain the petrogenesis of this granitic intrusion and the origin of the uranium anomaly. Microscopically, quartz, alkali-feldspar, and plagioclase are the essential mineral constituents of the granite, with minor biotite, while monazite, apatite, xenotime, and zircon are accessory minerals. Geochemically, the silica- and alkali-rich granites show a highly fractionated character with “seagull-shaped” REE patterns and significant negative anomalies of Ba and Sr, along with low Zr/Hf and Nb/Ta ratios. The granite has positive zircon ε_Hf(t) values ranging from +12.7 to +14.5 and crustal model ages (T_DM2) of 259–376 Ma, indicating a Paleozoic juvenile crustal source. Uraninite and brannerite are the main radioactive minerals responsible for the uranium anomaly within the Kunduleng granite. Uraninite presents well-developed cubic crystals and occurs as tiny inclusions in quartz and K-feldspar with magmatic characteristics (e.g., elevated ThO₂, Y₂O₃, and REE₂O₃ contents and low CaO, FeO, and SiO₂ concentrations). The calculated U-Th-Pb chemical ages (135.4 Ma) are contemporaneous with the U-Pb zircon age (135.4–135.6 Ma) of the granite, indicating a magmatic genesis for uraninite. The granites are highly differentiated, and extreme magmatic fractionation might be the main mechanism for the initial uranium enrichment. Brannerite is relatively less abundant and typically forms crusts on ilmenite and rutile or it cements them, representing the local redistribution and accumulation of uranium.