Mississippi is plagued by high rates of chronic disease. Therefore, the purpose of this study was to examine the health-promoting behaviors of residents in the Mississippi Delta and Northwest Mississippi Region utilizing the Health-Promoting Lifestyle Profile II (HPLP II) to identify specific health-promoting behaviors and the factors that best predict the residents' engagement in health-promoting behaviors. A non-experimental, cross-sectional study was used to assess the health-promoting behaviors of residents in the Mississippi Delta and Northwest Mississippi Region. A total of 165 individuals completed the survey which revealed that spiritual growth and interpersonal relations were the two behaviors most often practiced by the residents and nutrition and physical activity were the least practiced behaviors. Regression analysis identified general health and education as the two main variables which best predicted the health-promoting behaviors of the participants in this study. General health and education were the significant predictors for the HPLP II total scale and all subscales except physical activity. General health and alcohol were the significant predictors for physical activity. Results from this study could help improve the burden of chronic disease in Mississippi by providing an understanding of the current health-promoting behaviors among residents in rural Mississippi. Understanding their health behaviors could help healthcare professionals develop culturally appropriate community health programs to meaningfully impact their lives.