The purpose of this study was to ascertain whether uses of music partially mediate the link between personality and music preference. Undergraduate students (N = 122) completed the following scales: The Brief Big Five Inventory, The Uses of Music Inventory, The Short Test of Music Preference, The Life Orientation Test Revised, The Beck Depression Inventory, and the Perceived Stress Scale. Openness to experience positively predicted preferences for reflective-complex (RC; e.g., jazz/blues) and intense-rebellious (IR; e.g., rock/metal) music and was inversely related to upbeat-conventional (UC; e.g., country/pop) music, whereas extraversion was positively related to preferences for energetic-rhythmic (ER; e.g., rap/soul) and UC genres. A link between trait optimism and ER music preference was fully mediated by the more prominent extraversion trait. The relationship between openness to experience and RC music preference was partially mediated by cognitive uses of music, with a marginally significant analysis indicating partial mediation of emotional uses of music for openness to experience and IR music preference. Trait neuroticism, perceived stress, and depression scores all correlated positively with emotional uses of music. The current findings support studying personality contextually alongside uses of music when investigating music preference and shed light on how negative affect may inform emotional uses of music.