The influence of radiation damage on chemical alteration and in situ elemental and isotopic analyses in zircons is evaluated in three ~155Ma granites that are associated with W–Sn polymetallic deposits in the Nanling area of southern China. A combined approach is described using SEM imaging, laser Raman spectroscopy, and ion microprobe analysis of oxygen isotope ratios, U–Pb ages, and trace elements, including H. Domains within single zircons can be classified into two groups based on cathodoluminescence (CL) intensity and U–Th concentrations. Type-I are single crystals or clearly defined cores with bright CL, having U<1400ppm and Th<800ppm; type-II are rims surrounding type-I cores or single crystals with dark or intermediate CL-intensity and have 2100–30,000ppm U and 900–6500ppm Th. Both types of zircon display oscillatory zonation. Type-I zircons show a narrow range of δ18Ozircon values (8.5–9.2‰), while type-II zircons have much greater variation of apparent δ18Ozircon values (1.4–8.6‰). Relative to type-I, type-II zircons are characterized by elevated trace-element concentrations (including U, Th, rare earth elements, Y, Hf, Fe and Ti, LaN>10), high cumulative α-dose and background-corrected 16OH/16O, decreased Th/U and Hf/Yb ratios, and deviation in 206Pb/238U ages (up to 70Ma) from the mean age (ca. 155Ma) of type-I zircons. Moreover, laser Raman results show that type-II zircons have much broader FWHM (full width half maximum=6.3–37.8cm−1) and decreased amplitudes for the ~1005cm−1 Raman peak, indicating that they are affected by significant radiation damage. The Raman-measured preserved radiation damage (DαP=0.01–0.49×1015α-decay events/mg) is less than the total alpha-dose (DαT=0.1–1.72×1015α-decay events/mg) for each zircon of type-I and type-II with FWHM<10cm−1, indicating that 30–80% of the total radiation damage experienced by most of these zircons has been annealed. We attribute the negative correlation of δ18O versus U, Th, Y, Hf, La and cumulative α-dose for type-II zircons to open-system behavior resulting from radiation damage of the zircon crystal structure. We interpret type-II zircons to originally represent crystallization from a late-stage granite melt that was enriched in magmatic fluids and incompatible elements. The wide range and low δ18O values recorded by most type-II zircon domains are the result of secondary alteration by fluids (perhaps hydrothermal) facilitated by radiation damage and open system chemical and isotopic exchange. This work shows that a combined approach using imaging, laser Raman and trace element analysis is effective for evaluating the influence of radiation damage and alteration of zircon. This protocol is necessary to evaluate the reliability of in situ oxygen isotopic and U–Pb ages. The 16OH/16O ratio is readily measured during SIMS analysis of oxygen isotopes and can be an effective parameter to monitor alteration of radiation-damaged domains in zircon.