Bimetallic single-atom catalysts have garnered substantial interest due to their extraordinary catalytic prowess, which arises from atomic-level synergistic effects that can significantly enhance hydrogen evolution reaction (HER) kinetics beyond the capabilities of monometallic single-atom catalysts. However, the fabrication of bimetallic single-atom catalysts remains a tremendous challenge. Herein, we introduce an in-situ reduction method to fabricate bimetallic single-atom catalysts anchored on hydrogenated molybdenum trioxide (HxMoO3, 0 < x ≤ 2). Intriguingly, HxMoO3 exhibits inherent reducing capabilities that facilitate the in-situ reduction of some metal ions to metallic single atoms in steps on its surface, thereby enabling the constructing of bimetallic single-atom structures. As a testament to this strategy, the prepared PtM/HxMoO3 catalysts (M = Ag, Au, Pd, Rh) with ultra-low noble metal loadings (wt% < 1%) on the nano-HxMoO3 support exhibit remarkable efficiency in HER. Outperforming both monometallic single-atom catalysts (M/HxMoO3) and commercial Pt/C, these catalysts demonstrate enhanced HER performance, and the PtPd/HxMoO3 exhibits outstanding performance with an overpotentials of 10 mV at 10 mA/cm2, Tafel slope of 36 mV/dec, and long-term durability in acidic media. The presence of Pt single-atom significantly enhances the electrochemical surface area (ECSA) and accelerates the kinetics of the HER for other metal single atoms.