Mobile phone use while driving (MPUWD) is an increasingly common form of distracted driving. Given its widespread prevalence, it is important for researchers to identify factors that may predict who is more likely to engage in this risky behavior. The current study investigates associations between MPUWD risk behaviors, domain-specific risk perceptions, and broad personality dimensions. An Italian community sample (n = 804) completed a survey regarding MPUWD risk perceptions and engagement in MPUWD, in addition to the HEXACO-PI-R, a broad six-factor personality inventory (honesty-humility, emotionality, extraversion, agreeableness, conscientiousness, openness to experience), and the DOSPERT, a six-factor domain-specific self-report risk-taking measure (health/safety, recreational, social, ethical, gambling, and investment). With respect to domain-specific risk taking, greater frequency of SMS use while driving most strongly was associated with greater risk taking for the health/safety, gambling, and ethical risk domains. Further, greater honesty-humility and conscientiousness, two traits related to cognitive control and risk behaviors, and to a lesser extent openness to experience, were associated with less frequent MPUWD, and positively associated with MPUWD risk perceptions. With growing public safety concern surrounding MPUWD, understanding associated personality factors is not only important for identifying psychological mechanisms underlying risk behavior, but also for more effective prevention and intervention programs.