Background: Alcohol, tobacco, marijuana use, and sexual behaviors are consistently reported by high school students in the United States and can contribute to reduced quality of life. Empirical research finds that many assets may act as a protective factor for adolescent risk behaviors. As such, the purpose of this study was to examine the associations of youth assets and adolescent engagement in alcohol, cigarette, marijuana use, and sexual behavior among students 14-18 years in a rural state. Methods: Participants consisted of a random sample of 834 students aged 14-18 years attending two public school districts in rural Tennessee. A survey that assessed behaviors, knowledge, and youth assets was administered to these students during the spring of the school year. Results: Analysis found that a large percentage of students had engaged in alcohol, tobacco, marijuana use, and sexual behaviors. Additionally, it was discovered that some youth assets such as future aspirations, parental expectations, and positive peer influence were associated with a lower prevalence of adolescent substance use and sexual behavior. Furthermore, assets seem to be more protective in this sample of 14-18 year olds for past 30 days behavior compared to ever having used a substance (i.e., alcohol, tobacco, marijuana) or ever having had sexual intercourse. Conclusions: The results suggest that substance use and sexual behaviors among adolescents vary by youth asset. As such, it is important to realize that interventions designed to reduce alcohol, tobacco, marijuana use, and sexual behavior using an asset development framework needs to be tailored. (Contains 5 tables.)