Granitic rocks are crucial in revealing continental crust formation and evolution. The classic S- and I-type granitoid classification (based upon metasedimentary vs. metaigneous protolith) is widely adopted, but is not always straightforward when diagnostic minerals (e.g., cordierite for S-type and amphibole for I-type) are absent. In this study, zircon oxygen isotope and water content were measured simultaneously with Secondary Ion Mass Spectrometry (SIMS) on I- and S-type granitoids from various tectonic settings, including the New England Orogens (NEO), the Diancangshan–Ailaoshan and the Himalayan orogens, and the South China Block. Our results indicate the S-type samples are characterized by lower water-in-zircon content (median 14–170 ppm) than the I-type samples (median 449–885 ppm). Also, inherited I-type zircon cores in S-type samples from the NEO have higher water-in-zircon content than the zircon rims, confirming the different water content between the two granitoid types. We propose that water-in-zircon content is a potential tool to distinguish I- and S-type granitoids. Nonetheless, the low water-in-zircon content of S-type granitoids has likely no correlation with high magma water content.