There is little research on the role of personality in musical expertise. We address this gap in the literature by using data from a large national study (N = 7,870) to examine how scores on 10 facets of the Big Five dimensions of personality predicted self-reported musical sophistication and performance on two behavioral tests (melodic memory and rhythm perception). Personality predicted musical sophistication even after controlling for demographic variables and musicianship, with Openness to Aesthetics the best trait predictor. Substance use also predicted musical sophistication for various subscales and the behavioral tests. These findings replicated in both musician and non-musician subgroups.