The bimetallic nanoparticles modified polymetallic oxides are considered to be an attractive method to improve sensing performance. In this study, Bi2MoO6 (BMO) microspheres with bimetallic PtPd modification were synthesized via facile ultrasonic reduction and further solvothermal methods. The samples were characterized by SEM, HRTEM, XPS and UV–vis methods. The results showed the sensor based on BMO-1.5% exhibited an excellent response value of 7.18–200 ppm carbon monoxide (CO), which was approximately 5.28-fold higher than that of the initial BMO sensor (1.36). It also exhibited rapid response/recovery time (12/12 s). The theoretical calculation results exhibited the adsorption energy of PtPd/BMO (−2.29 eV) for CO molecules was substantially lower than that of the initial BMO (−0.05 eV). Total and partial density of states was determined to investigate the interaction between PtPd and BMO. The significantly enhanced gas properties of BMO-based sensors were attributed to the strong metal-support interaction (SMSI) and the sensitization of Pt and Pd. The work provides a feasible strategy for the analysis of sensing mechanisms.