Surface-enhanced Raman scattering (SERS) is a non-destructive spectral analysis technique. It has the virtues of high detectivity and sensitivity, which have been extensively studied for low-trace molecule detection. In the choices of SERS substrate materials, low-cost and abundant reserved transition metal oxide/chalcogenide materials have been regarded as promising substitutes for noble metals; however, their inferior SERS enhancement severely limits their practical application. Herein, a class of MoS2/MoOx heterostructures have been demonstrated with significantly improved SERS performance. Experimentally, MoS2/MoOx heterostructures were prepared by precisely controlled oxidation of MoS2 nanospheres in an ultraviolet-ozone environment, and the optimal SERS substrate was obtained with 14 hours of ultraviolet-ozone irradiation. SERS measurements revealed superior SERS performance with a detection limit of 10-7 M (rhodamine 6G) and an enhancement factor of 7.477 × 106 (R6G@10-7 M) could be obtained. Finally, the intuitive SERS enhancement mechanism was investigated via energy band analysis. It revealed that the constructed heterostructures enhanced the electron-hole separation, and the electrons were successively transferred to the analytes and significantly promoted the molecular polarizability, improving the SERS performance.