In this study, we performed first principles calculations to explore the adsorption behavior, electronic structures, and magnetic properties of CO molecules on pristine transition metal (TM)-doped WSe2/graphene (WSe2/G) heterostructures with vacancy defects. Introducing the Se-vacancies and TM dopants (Ti, Cr, Ni, and Co) enhanced the adsorption stability of CO on WSe2/G. The adsorption mechanism of CO molecules on primordial WSe2/G was physisorption, with large interaction distances and small adsorption energies. However, when the CO molecules were adsorbed on the defected and TM-doped WSe2/G, the adsorption mechanism changed to chemisorption. The adsorption of TMs (Ti, Cr, Ni, and Co) on the WSe2/G heterostructures was systematically investigated to evaluate its potential for application in gas sensor devices. The recovery time of CO@Cr–WSe2/G after CO adsorption was suitable for CO detection gas sensors. The findings of our study provide new technical directions for developing CO gas sensor devices.