Reward deficit models of addiction posit weaknesses in reward sensitivity to be promotive of substance dependence, while the externalizing spectrum model views substance problems as arising in large part from a general disinhibitory liability. The current study sought to integrate these perspectives by testing for separate and interactive associations of disinhibition and reward dysfunction with interview-assessed substance use disorders (SUDs). Community and college adults (N = 199) completed a scale measure of trait disinhibition and performed a gambling-feedback task yielding a neural index of reward sensitivity, the 'Reward Positivity' (RewP). Disinhibition and blunted RewP independently predicted SUDs, and also operated synergistically, such that participants - in particular, men - with high levels of disinhibition together with blunted RewP exhibited especially severe substance problems. Though limited by its cross-sectional design, this work provides new information about the interplay of disinhibition, reward processing, and gender in SUDs and suggests important directions for future research.