Evidence associating doping behavior with Moral Disengagement (MD) has accumulated over recent years. However, to date, research examining links between MD and doping has not considered key theoretically-grounded influences and outcomes of MD. As such, there is a need for quantitative research in relevant populations that purposefully examines the explanatory pathways through which MD is thought to operate. Towards this end, the current study examined a conceptually-grounded model of doping behavior that incorporated empathy, doping self-regulatory efficacy (SRE), doping MD, anticipated guilt and self-reported doping/doping susceptibility. Participants were specifically recruited to represent four key physical-activity contexts and consisted of team- (n = 195) and individual- (n = 169) sport athletes and hardcore- (n = 125) and corporate- (n = 121) gym exercisers representing both genders (nmale = 371; nfemale = 239); self-reported lifetime prevalence of doping across the sample was 13.6%. Each participant completed questionnaires assessing the aforementioned variables. Structural equation modelling indicated strong support for all study hypotheses. Specifically, we established: (a) empathy and doping SRE negatively predicted reported doping; (b) the predictive effects of empathy and doping SRE on reported doping were mediated by doping MD and anticipated guilt; (c) doping MD positively predicted reported doping; (d) the predictive effects of doping MD on reported doping were partially mediated by anticipated guilt. Substituting self-reported doping for doping susceptibility, multisample analyses then demonstrated these predictive effects were largely invariant between males and females and across the four physical-activity contexts represented. These findings extend current knowledge on a number of levels, and in doing so aid our understanding of key psychosocial processes that may govern doping behavior across key physical-activity contexts.