The mineral beryl (Be3Al2(SiO3)6) has the most abundant phase with industrial value for extracting a critical metal—beryllium. Due to multi-stage, fluid-induced growth, individual beryl grains may yield complex geochemical records, revealing variations in the oxygen isotopes of the fluids from which they crystallize. Secondary ion mass spectrometry (SIMS) with high sensitivity and high spatial resolution represents a good tool for in situ isotopic analysis. SIMS oxygen analyses require matrix-matched reference materials to calibrate instrumental mass fractionations during measurement. In this work, the oxygen isotope homogeneities of six beryl samples with different compositions (BS1, BS2, BS3, BS4, BS5, and BS6) were documented by SIMS. These samples’ recommended oxygen isotope compositions were characterized by laser fluorination isotope ratio mass spectrometry (IRMS). This study suggests that there is no matrix effect related to composition variation in beryl SIMS oxygen isotope analysis. The recommended δ18O values of the four reference materials, BS1, BS2, BS4, and BS5, were 15.01 ± 0.34‰ (2 standard deviations, 2 SD), 7.53 ± 0.16‰ (2 SD), 2.38 ± 0.14‰ (2 SD), and 10.72 ± 0.44‰ (2 SD), respectively. Therefore, BS1, BS2, BS4, and BS5 are recommended as suitable reference materials for in situ mineral beryl oxygen isotope microanalysis.