Abstract Quantitative Laser-Induced Breakdown Spectroscopy (LIBS) under high vacuum is important for in situ diagnostics of plasma–wall interactions (PWI) in nuclear fusion devices. In this work, we proposed a Pure-Element Spectral Matching (PESM) method for full-spectrum quantitative LIBS analysis under vacuum conditions. In PESM, LIBS spectra of pure Fe, Cr, Ni, and Mo acquired under identical conditions were used as basis components, and alloy spectra were reconstructed through global spectral fitting to directly estimate elemental atomic fractions. The method was validated using Mo-containing Ni-based alloy reference materials at a pressure of 5×10−3 Pa. Compared with the univariate calibration method and Partial Least Squares (PLS) models, PESM achieved superior quantitative performance for four-element analysis, with an overall RMSE of 1.55%, MAE of 1.33%, and MAPE of 7.01% (averaged over all elements). By operating on the full spectrum, PESM avoids manual spectral-line selection and peak integration, thereby reducing operator-dependent uncertainty while retaining broader spectral information. These results demonstrated that PESM was a practical and calibration-light strategy for vacuum LIBS quantification and showed strong potential for fusion-relevant PWI diagnostics.